Synergistic Effect of Ferroptosis-Inducing Nanoparticles and X-Ray Irradiation Combination Therapy.

Ferroptosis, characterized by the induction of cell death via lipid peroxidation, has been actively studied over the last few years and has shown the potential to improve the efficacy of cancer nanomedicine in an iron-dependent manner. Radiation therapy, a common treatment method, has limitations as a stand-alone treatment due to radiation resistance and safety as it affects even normal tissues. Although ferroptosis-inducing drugs help alleviate radiation resistance, there are no safe ferroptosis-inducing drugs that can be considered for clinical application and are still in the research stage. Here, the effectiveness of combined treatment with radiotherapy with Fe and hyaluronic acid-based nanoparticles (FHA-NPs) to directly induce ferroptosis, considering the clinical applications is reported. Through the induction of ferroptosis by FHA-NPs and apoptosis by X-ray irradiation, the therapeutic efficiency of cancer is greatly improved both in vitro and in vivo. In addition, Monte Carlo simulations are performed to assess the physical interactions of the X-rays with the iron-oxide nanoparticle. The study provides a deeper understanding of the synergistic effect of ferroptosis and X-ray irradiation combination therapy. Furthermore, the study can serve as a valuable reference for elucidating the role and mechanisms of ferroptosis in radiation therapy.

Importance of Local Ablative Therapies for Lung Metastases in Patients With Colorectal Cancer.

OBJECTIVE: To assess the effect of local ablative therapy (LAT) on overall survival in patients with lung metastases from colorectal cancer (CRC) compared with patients treated with systemic therapy. SUMMARY BACKGROUND DATA: CRC affects approximately 1.4 million individuals worldwide every year. The lungs are commonly affected by CRC, and there is no treatment standard for a secondary lung metastasis from CRC. METHODS: This longitudinal, retrospective cohort study (2010-2018) quantified the pulmonary and extrapulmonary tumor burden of 1143 patients by retrospectively reviewing computed tomography images captured at diagnosis. A comprehensive multidisciplinary approach informed how and when surgery and/or stereotactic body radiotherapy was administered. RESULTS: Among 1143 patients, 473 patients (41%) received LAT, with surgery first (n = 421) or stereotactic ablative radiation therapy first (n = 52) either at the time of diagnosis (n = 288), within 1 year (n = 132), or after 1 year (n = 53). LAT was repeated in 158 patients (33.4%, 384 total sessions) when new lung metastases were detected. The 5- and 10-year survival rates for patients treated with LAT (71.2% and 64.0%, respectively) were significantly higher than those of patients treated with systemic therapy alone (14.2% and 10.0%, respectively; P <0.001). The overall survival of patients who received LAT intervention increased as the total tumor burden decreased. CONCLUSIONS: A high long-term survival rate was achievable in a significant portion of patients with lung metastasis from CRC by the timely administrations of LAT to standard systemic therapy. The tumor burden and LAT feasibility should be included in a discussion during the follow-up period.

MRI Radiomics Model Predicts Pathologic Complete Response of Rectal Cancer Following Chemoradiotherapy.

Background Preoperative assessment of pathologic complete response (pCR) in locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT) is increasingly needed for organ preservation, but large-scale validation of an MRI radiomics model remains lacking. Purpose To evaluate radiomics models based on T2-weighted imaging and diffusion-weighted MRI for predicting pCR after nCRT in LARC and compare their performance with visual assessment by radiologists. Materials and Methods This retrospective study included patients with LARC (clinical stage T3 or higher, positive nodal status, or both) who underwent post-nCRT MRI and elective resection between January 2009 and December 2018. Surgical histopathologic analysis was the reference standard for pCR. Radiomic features were extracted from the volume of interest on T2-weighted images and apparent diffusion coefficient (ADC) maps from post-nCRT MRI to generate three models: T2 weighted, ADC, and both T2 weighted and ADC (merged). Radiomics signatures were generated using the least absolute shrinkage and selection operator with tenfold cross-validation. Three experienced radiologists independently rated tumor regression grades at MRI and compared these with the radiomics models' diagnostic outcomes. Areas under the curve (AUCs) of the radiomics models and pooled readers were compared by using the DeLong method. Results Among 898 patients, 189 (21%) achieved pCR. The patients were chronologically divided into training (n = 592; mean age ± standard deviation, 59 years ± 12; 388 men) and test (n = 306; mean age, 59 years ± 12; 190 men) sets. The radiomics signatures of the T2-weighted, ADC, and merged models demonstrated AUCs of 0.82, 0.79, and 0.82, respectively, with no evidence of a difference found between the T2-weighted and merged models (P = .49), while the ADC model performed worse than the merged model (P = .02). The T2-weighted model had higher classification performance (AUC, 0.82 vs 0.74 [P = .009]) and sensitivity (80.0% vs 15.6% [P < .001]), but lower specificity (68.4% vs 98.6% [P < .001]) than the pooled performance of the three radiologists. Conclusion An MRI-based radiomics model showed better classification performance than experienced radiologists for diagnosing pathologic complete response in patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Taylor in this issue.

First-line pembrolizumab versus dabrafenib/trametinib treatment for BRAF V600-mutant advanced melanoma.

BACKGROUND: Limited data are available to assist the selection between immune checkpoint inhibitors and BRAF/mitogen-activated protein kinase kinase inhibitors as first-line treatment for patients with BRAF-mutant advanced malignant melanoma. OBJECTIVE: To investigate the outcomes associated with first-line pembrolizumab or dabrafenib/trametinib treatment for advanced melanoma with activating BRAF V600 mutation. METHODS: Data of patients with BRAF V600-mutant melanoma who were treated with first-line pembrolizumab (n = 40) or dabrafenib/trametinib (n = 32) were analyzed. Tumor response, progression-free survival, and overall survival were evaluated. Immune evasion accompanied with emerging resistance to BRAF/mitogen-activated protein kinase kinase inhibitors was assessed. RESULTS: A longer overall survival was observed after first-line pembrolizumab treatment than after first-line dabrafenib/trametinib treatment (hazard ratio = 2.910, 95% CI: 1.552-5.459), although there were no significant differences in progression-free survival (P = .375) and response rate (P = .123). Emergence of resistance to dabrafenib/trametinib co-occurred with immune evasion, enabling melanoma cells to escape recognition and killing by Melan-A-specific CD8+ T cells. LIMITATIONS: Analysis was conducted in a retrospective manner. CONCLUSION: Pembrolizumab may be recommended over BRAF/mitogen-activated protein kinase kinase inhibitors as the first-line treatment in patients with advanced BRAF V600-mutant melanoma.

Prognostic impact of neutrophilia and lymphopenia on survival in anal cancer treated with definitive concurrent chemoradiotherapy: a retrospective multicenter study.

PURPOSE: This study evaluated the prognostic value of leukocyte, lymphocyte, and neutrophil counts in anal cancer patients undergoing concurrent chemoradiotherapy (CCRT). METHODS: Multi-institutional retrospective data review included 148 non-metastatic anal cancer patients treated with definitive CCRT with 5-fluorouracil plus mitomycin C between the year 2001 and 2019. The median radiation dose to the primary tumor was 54 Gy with a median pelvic dose of 45 Gy. Median follow-up duration was 56 months, and complete blood cell counts were analyzed from baseline to 1 year after the completion of radiotherapy. RESULTS: Although most patients showed a normal number of blood cells before treatment, 6.1% and 4.1% of patients showed leukocytosis (> 10,000/µl) and neutrophilia (> 7500/µl), respectively. After the initiation of treatment, seven patients (4.7%) displayed grade 4 lymphopenia (< 200/µl) at 1 month. Patients with initial leukocytosis showed inferior progression- and locoregional progression-free survival, and neutrophilia was a prognostic factor in all survival outcomes. Grade 4 lymphopenia at 1 month was also significantly associated with overall, progression-, and distant metastasis-free survival. On multivariate analyses, baseline neutrophilia was associated with 56.8-, 22.6-, 10.7-, and 23.0-fold increased risks of death, disease relapse, locoregional progression, and distant metastasis, respectively. Furthermore, lymphocytes < 200/µl at 1 month was linked to 6.8-, 5.4-, and 6.3-fold increased risks for death, disease relapse, and distant metastasis, respectively. CONCLUSION: The number of leukocytes, lymphocytes, and neutrophils readily acquired from routine blood tests before and during treatment could be an independent prognostic factor of survival in patients with anal cancer.

Simple calculation using anatomical features on pre-treatment verification CT for bladder volume estimation during radiation therapy for rectal cancer.

BACKGROUND: Despite detailed instruction for full bladder, patients are unable to maintain consistent bladder filling during a 5-week pelvic radiation therapy (RT) course. We investigated the best bladder volume estimation procedure for verifying consistent bladder volume. METHODS: We reviewed 462 patients who underwent pelvic RT. Biofeedback using a bladder scanner was conducted before simulation and during treatment. Exact bladder volume was calculated by bladder inner wall contour based on CT images (Vctsim). Bladder volume was estimated either by bladder scanner (Vscan) or anatomical features from the presacral promontory to the bladder base and dome in the sagittal plane of CT (Vratio). The feasibility of Vratio was validated using daily megavoltage or kV cone-beam CT before treatment. RESULTS: Mean Vctsim was 335.6 ± 147.5 cc. Despite a positive correlation between Vctsim and Vscan (R2 = 0.278) and between Vctsim and Vratio (R2 = 0.424), Vratio yielded more consistent results than Vscan, with a mean percentage error of 26.3 (SD 19.6, p < 0.001). The correlation between Vratio and Vctsim was stronger than that between Vscan and Vctsim (Z-score: - 7.782, p < 0.001). An accuracy of Vratio was consistent in megavoltage or kV cone-beam CT during treatment. In a representative case, we can dichotomize for clinical scenarios with or without bowel displacement, using a ratio of 0.8 resulting in significant changes in bowel volume exposed to low radiation doses. CONCLUSIONS: Bladder volume estimation using personalized anatomical features based on pre-treatment verification CT images was useful and more accurate than physician-dependent bladder scanners. TRIAL REGISTRATION: Retrospectively registered.

Nomogram for prediction of pathologic complete remission using biomarker expression and endoscopic finding after preoperative chemoradiotherapy in rectal cancer.

OBJECTIVE: The aim of this study is to develop a nomogram for prediction of pathologic complete remission (pCR) after preoperative chemoradiotherapy (CRT) for rectal cancer. METHODS: mRNA expression levels of seven molecular markers [p53, p21, Ki-67, vascular endothelial growth factor (VEGF), CD133, CD24, CD44] were measured by reverse transcriptase polymerase chain reaction (RT-PCR) in 120 rectal cancers. Endoscopic findings of clinical complete remission (cCR) and biologic variables were used to construct nomogram in the training group (n=80), which was validated in the validation group (n=40). RESULTS: mRNA expression levels of four markers (p53, p21, Ki67, CD133) correlated with pCR (24/80, 30.0%) in the training group. Low expression of p53 and/or high expression of p21, Ki67 and CD133 showed greater pCR rate. pCR was shown in 18 (69.2%) of 26 cases showing endoscopic cCR in the training group. Higher pCR rate was demonstrated in lower tumor location than middle tumor (19/49, 38.8% vs. 5/31, 16.1%). A nomogram for prediction of pCR was developed from the multivariate prediction model using these six variables, which showed good discrimination ability in the training group [area under the curve (AUC)=0.945] and validation group (AUC=0.922). The calibration plot showed good agreement between actual and predicted pCR in both patient groups. CONCLUSIONS: Nomogram for assessment of pCR can be useful for making treatment decisions after CRT according to predicted responses.

Efficacy of stereotactic body radiotherapy for unresectable or recurrent cholangiocarcinoma: a meta-analysis and systematic review.

PURPOSE: Non-surgical treatment including stereotactic body radiation therapy (SBRT) have been used practically as alternative modalities for unresectable or recurrent cholangiocarcinoma (CC). We performed a systematic review and meta-analysis to examine the efficacy of SBRT for such patients. METHODS: Embase, PubMed, MEDLINE, and Cochrane library databases were searched systematically until October 2017. Primary endpoint was 1­year local control (LC) rate; 1­year overall survival (OS), response rates, and grade ≥3 toxicities were assessed as secondary endpoints. RESULTS: Eleven studies (226 patients) were included. The prescribed median SBRT dose was 45 (range 30-55) Gy in 3-5 fractions. The pooled 1­year LC rate was 81.8% (95% confidence interval [CI] 69.4-89.9%) in the studies using an equivalent dose in 2 Gy per fraction (EQD2) ≥71.3 Gy2 and 74.7% (95% CI 57.1-86.7%) in the studies using an EQD2 <71.3 Gy2. The median OS was 13.6 (range 10-35.5) months. The pooled 1­year OS rate was 53.8% (95% CI 44.9-62.5%) and the pooled 1­year LC rate was 78.6% (95% CI 69.0-85.8%). Most common toxicity was duodenal ulcer and gastric ulcer in available studies, with the acute incidence of grade ≥3 of less than 10% and the late incidence of 10-20%. CONCLUSIONS: SBRT was a feasible treatment option with respect to achieving a high LC for unresectable or recurrent CC. Gastrointestinal toxicity is acceptable, but remains an obstacle related to dose escalation.

Long-term outcome, relapse patterns, and toxicity after radiotherapy for orbital mucosa-associated lymphoid tissue lymphoma: implications for radiotherapy optimization.

OBJECTIVES: Although mucosa-associated lymphoid tissue lymphoma (MALToma) is sensitive to radiation therapy (RT), the optimal RT dose and treatment volumes have not been established. This study aimed to assess the relapse patterns and outcomes of patients with orbital MALToma who underwent RT and to suggest implications for optimized RT. METHODS: We reviewed 212 patients (246 orbits) diagnosed with orbital MALToma who received RT between 1993 and 2013. Median RT dose was 25.2 Gy. Generally, conjunctival and eyelid lesions were irradiated with electrons, whereas retrobulbar and lacrimal gland lesions with photons. Lens shielding was used for 70% of treated eyes, mainly conjunctival and eyelid tumors. RESULTS: Relapse occurred in 29 patients. Among 11 patients with local relapse (LR), 4 were attributed to insufficient dose (n = 2) and improper RT volume (n = 2). The 10-year LR, contralateral orbit relapse, and distant relapse rates were 8.6%, 12.8% and 4.9%, respectively. Twelve patients died of disease-specific causes (n = 1) and intercurrent diseases (n = 11). The 10-year relapse-free survival, overall survival, and cause-specific survival rates were 69.7%, 88.2% and 98.8%, respectively. Grade 3 cataracts and nasolacrimal duct obstruction were observed in 27 and 4 orbits, respectively. CONCLUSION: Low-dose RT with proper lens shielding is an appropriate treatment for orbital MALToma in terms of high disease control rate and acceptable morbidity. However, lower RT dose may be attempted to further reduce toxicity while maintaining excellent outcomes.

Radiotherapy is a safe and effective salvage treatment for recurrent cervical cancer.

OBJECTIVE: The feasibility of salvage radiotherapy (RT) for patients with recurrent cervical cancer after definitive treatment is contentious. The purpose of this study was to investigate the feasibility and benefit of RT, particularly intensity-modulated RT (IMRT), for salvage treatment in patients with recurrent cervical cancer. METHODS: We retrospectively analyzed 125 patients with recurrent cervical cancer treated with RT at Yonsei Cancer Center between January 2007 and December 2016. All patients received salvage RT for the recurred or metastatic tumor mass. Irradiating dose and volume were determined depending on initial treatment. IMRT was selected in challenging cases, such as re-irradiation or for patients for whom implementing a satisfactory 3-dimensional conformal RT plan was challenging. RESULTS: The median follow-up period was 5.5 years (range, 10.8 months to 41 years). The 5-year local failure-free survival (LFFS) and progression-free survival (PFS) rates were 63.9% and 39.6%, respectively. The 5-year overall survival (OS) rate was 66%; 10-year OS reached 51%. The median PFS rates in patients with locoregional failure, distant metastases, or both were 45.4, 29.1, and 14.7 months, respectively (p = 0.005). For the 45 patients that received re-irradiation, 5-year LFFS, PFS, and OS rates were 47.1%, 33.2%, and 66.5%, respectively. Late complications were observed in 12 patients (12/125, 9.6%). CONCLUSIONS: Our data suggest that salvage RT is safe and effective against recurrent cervical cancer. IMRT is a safe and effective salvage modality for these patients, including those requiring re-irradiation.

T2-weighted signal intensity-selected volumetry for prediction of pathological complete response after preoperative chemoradiotherapy in locally advanced rectal cancer.

OBJECTIVES: To evaluate the diagnostic value of signal intensity (SI)-selected volumetry findings in T2-weighted magnetic resonance imaging (MRI) as a potential biomarker for predicting pathological complete response (pCR) to preoperative chemoradiotherapy (CRT) in patients with rectal cancer. METHODS: Forty consecutive patients with pCR after preoperative CRT were compared with 80 age- and sex-matched non-pCR patients in a case-control study. SI-selected tumor volume was measured on post-CRT T2-weighted MRI, which included voxels of the treated tumor exceeding the SI (obturator internus muscle SI + [ischiorectal fossa fat SI - obturator internus muscle SI] × 0.2). Three blinded readers independently rated five-point pCR confidence scores and compared the diagnostic outcome with SI-selected volumetry findings. The SI-selected volumetry protocol was validated in 30 additional rectal cancer patients. RESULTS: The area under the receiver-operating characteristic curve (AUC) of SI-selected volumetry for pCR prediction was 0.831, with an optimal cutoff value of 649.6 mm3 (sensitivity 0.850, specificity 0.725). The AUC of the SI-selected tumor volume was significantly greater than the pooled AUC of readers (0.707, p < 0.001). At this cutoff, the validation trial yielded an accuracy of 0.87. CONCLUSION: SI-selected volumetry in post-CRT T2-weighted MRI can help predict pCR after preoperative CRT in patients with rectal cancer. KEY POINTS: • Fibrosis and viable tumor MRI signal intensities (SIs) are difficult to distinguish. • T2 SI-selected volumetry yields high diagnostic performance for assessing pathological complete response. • T2 SI-selected volumetry is significantly more accurate than readers and non-SI-selected volumetry. • Post-chemoradiation therapy T2-weighted MRI SI-selected volumetry facilitates prediction of pathological complete response.

Metabolic positron emission tomography parameters predict failure patterns in early non-small-cell lung cancer treated with stereotactic body radiation therapy: a single institution experience.

OBJECTIVE: The prognostic value of metabolic parameters using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has not been established for early non-small cell lung cancer (NSCLC). Accordingly, the authors investigated the prognostic value of metabolic parameters in terms of failure patterns in patients with early NSCLC who underwent stereotactic body radiation therapy (SBRT). METHODS: Data from 35 patients with Stage I NSCLC who underwent SBRT using CyberKnife and received pretreatment FDG PET/CT between 2008 and 2016 were retrospectively reviewed. Maximum standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis were measured. The significance of these parameters with regard to failure patterns was assessed. RESULTS: The median follow-up was 23 months for all patients and 34 months for living patients. Ten patients experienced recurrence: three local failures, five regional failures (RF), and eight distant failures (DF). Three-year local, regional and distant control rates were 96.7%, 86.4% and 71.1%, respectively. High SUVmax (<9 vs. ≥9) was an independent predictive factor associated with increased RF (P = 0.027) and DF (P = 0.008). Furthermore, SUVmax was indicative of both progression-free (P = 0.015) and overall (P = 0.034) survival. CONCLUSIONS: High SUVmax was a significant metabolic parameter associated with increased RF and DF in patients with early NSCLC who received SBRT, having a high propensity for dissemination. These results suggest that adjuvant treatment in conjunction with SBRT may be considered in patients with early NSCLC and high SUVmax.

The role of endoscopic evaluation for radiation proctitis in patients receiving intermediate-dose postoperative radiotherapy for rectal cancer.

OBJECTIVES: High-dose pelvic radiotherapy (RT) is known to be associated with chronic radiation proctitis (RP). However, the effects of intermediate radiation doses are unknown. We assessed the incidence of late clinical RP among patients with rectal cancer receiving intermediate-dose postoperative RT, as well as the role of early endoscopic abnormalities in predicting RP development. METHODS: We retrospectively reviewed 153 patients with rectal cancer who received postoperative RT at a median dose of 54 Gy between 2005 and 2009 and who underwent endoscopic examination within 12 months thereafter. Endoscopic RP was assessed using the Vienna rectoscopy score (VRS). Late clinical RP toxicity was evaluated, as was its correlation with endoscopic RP. RESULTS: All patients underwent an endoscopic examination at a median of 9 months after postoperative pelvic RT. Endoscopic RP was detected in 45 patients (29.4%); the predominant patterns were telangiectasia and congested mucosa. During the median 88-month follow-up period, 29 patients (19.0%) experienced late clinical RP; only 3 (2.0%) had Grade 3 or above. The VRS predicted the development of late clinical RP as well as its cumulative incidence (P < 0.001). Endoscopic evidence of telangiectasia was significantly associated with the development of late clinical RP (P < 0.001). CONCLUSIONS: Early endoscopic findings using VRS are useful for predicting the possibility of late clinical RP, although the incidences of severe cases were low. Patients with endoscopic abnormalities should be followed closely owing to their susceptibility to clinical RP.

A Survey of Radiation Therapy Utilization in Korea from 2010 to 2016: Focusing on Use of Intensity-Modulated Radiation Therapy.

BACKGROUND: This study aimed to assess the recent changes of radiation therapy (RT) modalities in Korea. In particular, we focused on intensity-modulated radiation therapy (IMRT) utilization as the main index, presenting the application status of advanced RT. METHODS: We collected information from the Korean Health and Insurance Review and Assessment Service data based on the National Health Insurance Service claims and reimbursements records by using treatment codes from 2010 to 2016. We classified locating region of each institution as capital vs. non-capital areas and metropolitan vs. non-metropolitan areas to assess the regional difference in IMRT utilization in Korea. RESULTS: IMRT use has been steadily increased in Korea, with an annual increase estimate (AIE) of 37.9% from 2011 to 2016 (P < 0.001) resulting in IMRT being the second most common RT modality following three-dimensional conformal radiotherapy. In general, an increasing trend of IMRT utilization was observed, regardless of the region. The rate of AIE in the capital areas or metropolitan areas was higher than that in non-capital areas or non-metropolitan areas (40.7% vs. 31.9%; P < 0.001 and 39.7% vs. 29.4%; P < 0.001, respectively). DISCUSSION: The result of our survey showed that IMRT has become one of the most common RT modalities. IMRT is becoming popular in both metropolitan and non-metropolitan areas, while metropolitan area has faster AIE possibly due to concentration of medical resources and movement of advanced patients.

Rectal Mucinous Adenocarcinoma: MR Imaging Assessment of Response to Concurrent Chemotherapy and Radiation Therapy-A Hypothesis-generating Study.

Purpose To develop a system for assessment of tumor regression grade (TRG) with magnetic resonance (MR) imaging that is applicable to rectal mucinous adenocarcinoma (RMAC) and to obtain a preliminary evaluation of the association of MR imaging assessment of TRG with response to preoperative concurrent chemotherapy and radiation therapy (CCRT). Materials and Methods This retrospective study was approved by the institutional review board, and informed consent was waived. Pre- and post-CCRT MR images of 59 patients with RMAC (median age, 59 years; range, 29-80 years; 42 men [median age, 59 years; range, 36-80 years] and 17 women [median age, 57 years; range, 29-79 years]) who underwent CCRT and subsequent elective resection from July 2005 to June 2015 were analyzed. Two experienced gastrointestinal radiologists independently analyzed imaging parameters such as T stage, mesorectal fascia status, extramural vascular invasion status, and TRG by using modified criteria developed for assessment of RMAC. Interobserver variability was calculated with weighted κ analysis, and disagreement was settled in consensus. MR imaging TRG results were compared with those from pathologic TRG analysis (Mandard grade). Logistic regression analyses were performed to evaluate associations between imaging parameters and pathologic TRG. Results There was moderate to substantial agreement for imaging parameters (post-CCRT T stage-weighted κ, 0.7134; post-CCRT mesorectal fascia status, 0.618; TRG, 0.5023). Modified MR imaging TRG results were significantly associated with pathologic responsiveness (responsive group, Mandard grade 1 or 2; nonresponsive group, Mandard grades 3-5; P = .023). Results of univariate and multivariate logistic regression analyses indicated that MR imaging TRG was the only factor significantly associated with CCRT responsiveness (univariate analysis, P = .023; multivariate analysis, P = .0261). Conclusion The modified MR imaging assessment of TRG was associated with treatment response to CCRT in patients with RMAC. © RSNA, 2017 Online supplemental material is available for this article.

Preoperative Serum Carcinoembryonic Antigen Level as a Prognostic Factor for Recurrence and Survival After Curative Resection Followed by Adjuvant Chemotherapy in Stage III Colon Cancer.

BACKGROUND: Carcinoembryonic antigen (CEA) is the most widely used tumor marker in colon cancer; however, there has been controversy regarding the significance of preoperative serum CEA level as a prognostic factor for recurrence. In this study, we evaluated the optimal cutoff value and prognostic significance of preoperative serum CEA level in stage III colon cancer. METHODS: Based on a retrospective cohort of 965 patients with stage III colon cancer who underwent elective curative surgery and adjuvant chemotherapy with fluoropyrimidine and oxaliplatin (training set), we determined the optimal cutoff value of CEA for recurrence using the Contal and O'Quigley method. We assessed the prognostic value of this cutoff value in terms of disease-free survival (DFS) and overall survival (OS) in a prospective cohort of 268 patients with stage III colon cancer (validation set). A Cox proportional hazards model was used to explore the association of prognostic variables with DFS and OS. RESULTS: The statistically determined best cutoff value for CEA was 3 ng/mL in the training set. A high CEA level (≥3 ng/mL) was associated with inferior DFS (hazard ratio [HR] 4.609, 95 % confidence interval [CI] 2.028-10.474) and OS (HR 3.956, 95 % CI 1.127-13.882) in the validation set, while multivariate analysis showed that a high CEA level was an independent risk factor for DFS and OS in both study subsets. CONCLUSION: Preoperative serum CEA level is an independent prognostic factor for DFS and OS in patients with stage III colon cancer after curative resection and adjuvant chemotherapy.

Role of adjuvant chemotherapy in locally advanced rectal cancer with ypT0-3N0 after preoperative chemoradiation therapy and surgery.

BACKGROUND: We aimed to explore the clinical benefit of adjuvant chemotherapy (AC) with fluoropyrimidine in patients with ypT0-3N0 rectal cancer after preoperative chemoradiation therapy (CRT) followed by total mesorectal excision (TME). METHODS: Patients with ypT0-3N0 rectal cancer after preoperative CRT and TME were included using prospectively collected tumor registry cohort between January 2001 and December 2013. Patients were categorized into two groups according to the receipt of AC. Disease-free survival (DFS) and overall survival (OS) were compared between the adjuvant and observation groups. To control for potential confounding factors, we also calculated propensity scores and performed propensity score-matched analysis for DFS and OS. RESULTS: Of the 339 evaluated patients, 87 patients (25.7%) did not receive AC. There were no differences in DFS (hazard ratio [HR], 0.921; 95% confidence interval [CI], 0.562-1.507; P = 0.742) and OS (HR, 0.835; 95% CI, 0.423-1.648; P = 0.603) between the adjuvant and observation groups. After propensity score matching, DFS (HR, 1.129; 95% CI, 0.626-2.035; P = 0.688) and OS (HR, 1.200; 95% CI, 0.539-2.669; P = 0.655) did not differ between the adjuvant and observation groups. Advanced T stage and positive resection margin were independently associated with inferior DFS and OS on multivariate analysis. CONCLUSIONS: AC did not improve DFS and OS for patients with ypT0-3N0 rectal cancer after preoperative CRT followed by TME in this cohort study. The confirmative role of AC in locally advanced rectal cancer should be evaluated in prospective randomized trials with a larger sample size.

Art therapy based on appreciation of famous paintings and its effect on distress among cancer patients.

PURPOSE: We aimed to evaluate the effectiveness of art therapy based on appreciation of famous paintings on the distress of cancer patients receiving radiotherapy. In particular, we focused on anxiety, depression, and cancer-related symptoms. METHODS: Between October 2015 and February 2016, cancer patients receiving radiotherapy were recruited prospectively to participate in the art therapy based on famous painting appreciation. The art therapy took place in two parts comprising 4 sessions of famous painting appreciation and 4 sessions of creative artwork generation; these sessions were performed twice weekly over four weeks. Cancer-related distress was measured using the Hospital Anxiety and Depression Scale (HADS), Hamilton Depression Rating Scale (HDRS), and Edmonton Symptom Assessment Scale (ESAS) at three points: before the art therapy began, after the fourth session of art therapy, and after the eighth session. RESULTS: Of the 24 enrolled patients, 20 (83%) completed all eight sessions. We observed significant improvements in HADS anxiety and total scores over time according to linear mixed models with Bonferroni corrections (all p < 0.05). Furthermore, HDRS scores demonstrated significant decreases according to linear mixed models (p = 0.001). Fewer patients met the HADS or HDRS criteria for severe anxiety or depression after the intervention. We observed no changes in ESAS mean scores. CONCLUSIONS: Art therapy based on famous painting appreciation significantly improved cancer-related anxiety and depression and reduced the prevalence of severe anxiety and depression during cancer treatment.

Cell Microarray Technologies for High-Throughput Cell-Based Biosensors.

Due to the recent demand for high-throughput cellular assays, a lot of efforts have been made on miniaturization of cell-based biosensors by preparing cell microarrays. Various microfabrication technologies have been used to generate cell microarrays, where cells of different phenotypes are immobilized either on a flat substrate (positional array) or on particles (solution or suspension array) to achieve multiplexed and high-throughput cell-based biosensing. After introducing the fabrication methods for preparation of the positional and suspension cell microarrays, this review discusses the applications of the cell microarray including toxicology, drug discovery and detection of toxic agents.

Effects of microsatellite instability on recurrence patterns and outcomes in colorectal cancers.

BACKGROUND: Among colorectal cancers (CRCs), high-frequency microsatellite instability (MSI-H) is associated with a better prognosis, compared with low-frequency MSI or microsatellite stability (MSI-L/MSS). However, it is unclear whether MSI affects the prognosis of recurrent CRCs. METHODS: This study included 2940 patients with stage I-III CRC who underwent complete resection. The associations of MSI status with recurrence patterns, disease-free survival (DFS), overall survival from diagnosis to death (OS1), and overall survival from recurrence to death (OS2) were analysed. RESULTS: A total of 261 patients (8.9%) had MSI-H CRC. Patients with MSI-H CRC had better DFS, compared to patients with MSI-L/MSS CRC (hazard ratio (HR): 0.619, P<0.001). High-frequency microsatellite instability CRC was associated with more frequent local recurrence (30.0% vs 12.0%, P=0.032) or peritoneal metastasis (40.0% vs 12.3%, P=0.003), and less frequent lung (10.0% vs 42.5%, P=0.004) or liver metastases (15.0% vs 44.7%, P=0.01). Recurrent MSI-H CRC was associated with worse OS1 (HR: 1.363, P=0.035) and OS2 (HR: 2.667, P<0.001). An analysis of patients with colon cancer yielded similar results. CONCLUSIONS: Recurrence patterns differed between MSI-H CRC and MSI-L/MSS CRC, and recurrent MSI-H CRCs had a worse prognosis.