Prognostic Significance of Bulky Nodal Disease in Anal Cancer Management: A Multi Institutional Study.

Purpose: This study aimed to assess the prognostic significance of bulky nodal involvement in patients with anal squamous cell carcinoma treated with definitive chemoradiotherapy. Materials and Methods: We retrospectively analyzed medical records of patients diagnosed with anal squamous cell carcinoma who underwent definitive chemoradiotherapy at three medical centers between 2004 and 2021. Exclusion criteria included distant metastasis at diagnosis, 2D radiotherapy, and salvage treatment for local relapse. Bulky N+ was defined as nodes with a long diameter of 2 cm or greater. Results: A total of 104 patients were included, comprising 51 with N0, 46 with non-bulky N+, and 7 with bulky N+. The median follow-up duration was 54.0 months (range, 6.4-162.2 months). Estimated 5-year progression-free survival (PFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS) rates for patients with bulky N+ were 42.9%, 42.9%, and 47.6%, respectively. Bulky N+ was significantly associated with inferior PFS, LRRFS and OS compared to patients without or with non-bulky N+, even after multivariate analysis. We proposed a new staging system incorporating bulky N+ as N2 stage, with estimated 5-year LRRFS, PFS, and OS rates of 81.1%, 80.6%, and 86.2% for stage I, 67.7%, 60.9%, and 93.3% for stage II, and 42.9%, 42.9%, and 47.6% for stage III disease, enhancing the predictability of prognosis. Conclusion: Patients with bulky nodal disease treated with standard chemoradiotherapy experienced poor survival outcomes, indicating the potential necessity for further treatment intensification.

Exploring depressive symptom trajectories in COVID-19 patients with clinically mild condition in South Korea using remote patient monitoring: longitudinal data analysis.

Background: During the height of the COVID-19 pandemic, the Korean government temporarily allowed full scale telehealth care for safety and usability. However, limited studies have evaluated the impact of telehealth by analyzing the physical and/or mental health data of patients with COVID-19 diagnosis collected through telehealth targeting Korean population. Objective: This study aimed to identify subgroup of depressive symptom trajectories in patients with clinically mild COVID-19 using collected longitudinal data from a telehealth-based contactless clinical trial. Methods: A total of 199 patients with COVID-19 were accrued for contactless clinical trial using telehealth from March 23 to July 20, 2022. Depressive symptoms were measured using the patient health questionnaire-9 on the start day of quarantine, on the final day of quarantine, and 1 month after release from quarantine. Additionally, acute COVID-19 symptoms were assessed every day during quarantine. This study used a latent class mixed model to differentiate subgroups of depressive symptom trajectories and a logistic regression model with Firth's correction to identify associations between acute COVID-19 symptoms and the subgroups. Results: Two latent classes were identified: class 1 with declining linearity at a slow rate and class 2 with increasing linearity. Among COVID-19 symptoms, fever, chest pain, and brain fog 1 month after release from quarantine showed strong associations with class 2 (fever: OR, 19.43, 95% CI, 2.30-165.42; chest pain: OR, 6.55, 95% CI, 1.15-34.61; brain fog: OR, 7.03, 95% CI 2.57-20.95). Sleeping difficulty and gastrointestinal symptoms were also associated with class 2 (gastrointestinal symptoms: OR, 4.76, 95% CI, 1.71-14.21; sleeping difficulty: OR, 3.12, 95% CI, 1.71-14.21). Conclusion: These findings emphasize the need for the early detection of depressive symptoms in patients in the acute phase of COVID-19 using telemedicine. Active intervention, including digital therapeutics, may help patients with aggravated depressive symptoms.

Practice guidelines for managing extrahepatic biliary tract cancers.

Backgrounds/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Assessment of lymph node area coverage with total marrow irradiation and implementation of total marrow and lymphoid irradiation using automated deep learning-based segmentation.

BACKGROUND: Total marrow irradiation (TMI) and total marrow and lymphoid irradiation (TMLI) have the advantages. However, delineating target lesions according to TMI and TMLI plans is labor-intensive and time-consuming. In addition, although the delineation of target lesions between TMI and TMLI differs, the clinical distinction is not clear, and the lymph node (LN) area coverage during TMI remains uncertain. Accordingly, this study calculates the LN area coverage according to the TMI plan. Further, a deep learning-based model for delineating LN areas is trained and evaluated. METHODS: Whole-body regional LN areas were manually contoured in patients treated according to a TMI plan. The dose coverage of the delineated LN areas in the TMI plan was estimated. To train the deep learning model for automatic segmentation, additional whole-body computed tomography data were obtained from other patients. The patients and data were divided into training/validation and test groups and models were developed using the "nnU-NET" framework. The trained models were evaluated using Dice similarity coefficient (DSC), precision, recall, and Hausdorff distance 95 (HD95). The time required to contour and trim predicted results manually using the deep learning model was measured and compared. RESULTS: The dose coverage for LN areas by TMI plan had V100% (the percentage of volume receiving 100% of the prescribed dose), V95%, and V90% median values of 46.0%, 62.1%, and 73.5%, respectively. The lowest V100% values were identified in the inguinal (14.7%), external iliac (21.8%), and para-aortic (42.8%) LNs. The median values of DSC, precision, recall, and HD95 of the trained model were 0.79, 0.83, 0.76, and 2.63, respectively. The time for manual contouring and simply modified predicted contouring were statistically significantly different. CONCLUSIONS: The dose coverage in the inguinal, external iliac, and para-aortic LN areas was suboptimal when treatment is administered according to the TMI plan. This research demonstrates that the automatic delineation of LN areas using deep learning can facilitate the implementation of TMLI.

Safety and Efficacy of Neoadjuvant SABR in Pancreatic Cancer: Effect of Magnetic Resonance Imaging-Guided Respiratory-Gated Adaptive Radiation Therapy.

Purpose: We aimed to evaluate the safety and efficacy of neoadjuvant SABR using magnetic resonance imaging-guided respiratory-gated adaptive radiation therapy (MRgRg-ART) in pancreatic cancer. Methods and Materials: We performed a single-institution retrospective review in patients with pancreatic cancer who underwent neoadjuvant SABR followed by surgical resection. After neoadjuvant chemotherapy, those considered resectable by the multidisciplinary team received SABR over 5 consecutive days using MRgRg-ART. Factors associated with severe postoperative complications (Clavien-Dindo grade ≥III) and prognostic factors for overall survival were analyzed. Results: Sixty-two patients were included in the analysis, with a median follow-up of 10.3 months. The median prescribed dose to the planning target volume was 50 Gy. Fifty-two (85.3%) patients underwent R0 resection, and 11 (18.0%) experienced severe postoperative complications. No factors were associated with the incidence of severe postoperative complications. There were 3 cases of locoregional recurrence, resulting in a 12-month local control rate of 93.1%. Elevated postoperative carbohydrate antigen 19-9 was significantly associated with poor overall survival in the multivariate analysis (P = .037). Conclusions: Neoadjuvant SABR with 50 Gy using MRgRg-ART delivered to pancreatic cancer resulted in a notable survival outcome with acceptable toxicities. Further studies are warranted to investigate the long-term effects of this method.

Risk Factors for Distant Metastasis in Extrahepatic Bile Duct Cancer after Curative Resection (KROG 1814).

PURPOSE: Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated. MATERIALS AND METHODS: Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated. RESULTS: After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors. CONCLUSION: Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.

Radiation Oncologists' Perspectives on Oligometastatic Disease: A Korean Survey Study.

PURPOSE: Perspectives of radiation oncologists on oligometastatic disease was investigated using multi-layered survey. MATERIALS AND METHODS: Online survey on the oligometastatic disease was distributed to the board-certified regular members of the Korean Society for Radiation Oncology. The questionnaire consisted of four domains: five questions on demographics; five on the definition of oligometastatic disease; four on the role of local therapy; and three on the oligometastatic disease classification, respectively. RESULTS: A total of 135 radiation oncologists participated in the survey. The median length of practice after board certification was 22.5 years (range, 1 to 44 years), and the vast majority (94.1%) answered affirmatively to the clinical experience in oligometastatic disease management. Nearly two-thirds of the respondents considered the number of involved organs as an independent factor in defining oligometastasis. Most frequently perceived upper limit on the numerical definition of oligometastasis was 5 (64.2%), followed by 3 (26.0%), respectively. Peritoneal and brain metastasis were nominated as the sites to be excluded from oligometastastic disease by 56.3% and 12.6% of the participants, respectively. Vast majority (82.1%) agreed on the role of local treatment in the management of oligometastatic disease. Majority (72%) of the participants acknowledged the European Society for Radiotherapy and Oncology (ESTRO)-European Organisation for Research and Treatment of Cancer (EORTC) classification of oligometastatic disease, however, only 43.3% answered that they applied this classification in their clinical practice. Underlying reasons against the clinical use were 'too complicated' (66.0%), followed by 'insufficient supporting evidence' (30.0%), respectively. CONCLUSION: While most radiation oncologists supported the role of local therapy in oligometastatic disease, there were several inconsistencies in defining and categorizing oligometastatic disease. Continued education and training on oligometastatic disease would be also required to build consensus among participating caregivers.

Predicting Deterioration from Wearable Sensor Data in People with Mild COVID-19.

Coronavirus has caused many casualties and is still spreading. Some people experience rapid deterioration that is mild at first. The aim of this study is to develop a deterioration prediction model for mild COVID-19 patients during the isolation period. We collected vital signs from wearable devices and clinical questionnaires. The derivation cohort consisted of people diagnosed with COVID-19 between September and December 2021, and the external validation cohort collected between March and June 2022. To develop the model, a total of 50 participants wore the device for an average of 77 h. To evaluate the model, a total of 181 infected participants wore the device for an average of 65 h. We designed machine learning-based models that predict deterioration in patients with mild COVID-19. The prediction model, 10 min in advance, showed an area under the receiver characteristic curve (AUC) of 0.99, and the prediction model, 8 h in advance, showed an AUC of 0.84. We found that certain variables that are important to model vary depending on the point in time to predict. Efficient deterioration monitoring in many patients is possible by utilizing data collected from wearable sensors and symptom self-reports.

The Clinical Efficacy of Colorectal Cancer Patients with Pulmonary Oligometastases by Sterotactic Body Ablative Radiotherapy: A Meta-Analysis.

Purpose: There is increasing interest in the efficacy of stereotactic ablative radiotherapy (SABR) for treating colorectal cancer (CRC) patients with oligometastases (OM), recently. The purpose of this meta-analysis was to evaluate local control (LC), progression-free survival (PFS), and overall survival (OS) of CRC patients with pulmonary OM treated with SABR and toxicities. Materials and Methods: Studies that reported SABR for CRC patients with pulmonary OM were searched from MEDLINE and EMBASE. Treatment outcomes including LC, PFS, OS, and toxicities of grade 3 or higher were assessed. Results: A total of 19 studies with 1,668 patients were chosen for this meta-analysis. Pooled 1-, 2-, and 3-year LC rates were 83.1%, 69.3%, and 63.9%, respectively. PFS rates were 44.8%, 26.5%, and 21.5% at 1, 2, and 3 years, respectively. OS rates at 1-, 2-, and 3-year were 87.5%, 69.9%, and 60.5%, respectively. The toxicity rate of grade 3 or higher was 3.6%. The effect of dose escalation was meta-analyzed using available studies. Conclusion: Application of SABR to CRC patients with pulmonary OM achieved modest local control with acceptable toxicity according to the present meta-analysis. Further studies establishing the clinical efficacy of SABR are guaranteed.

Total neoadjuvant therapy with short-course radiotherapy Versus long-course neoadjuvant chemoradiotherapy in Locally Advanced Rectal cancer, Korean trial (TV-LARK trial): study protocol of a multicentre randomized controlled trial.

BACKGROUND: For locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT) may enhance tumour response, reduce recurrence, and improve patient compliance compared to upfront surgery. Recent studies have shown that chemoradiotherapy (CRT) followed by consolidation chemotherapy leads to higher rate of pathologic complete response (pCR) than induction chemotherapy followed by CRT. However, an optimal TNT regimen that maximise the pCR rate and minimise toxicity has not been established. Therefore, the aim of this trial was to investigate whether preoperative short-course radiotherapy followed by chemotherapy with four cycles of CAPOX can double the pCR rate compared to a standard schedule of long-course preoperative CRT in patients with LARC. METHODS: This is a multi-centre, prospective, open label, randomised controlled trial. Patients with clinical primary tumour stage 3 and higher or regional node-involved rectal cancer located within 10 cm from the anal verge were randomly assigned equally to short-course radiotherapy (25 Gy in 5 fractions over 1 week) followed by four cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) (TNT) or CRT (50.4 Gy in 28 fractions over 5 weeks, concurrently with concomitant oral capecitabine 825 mg/m2 twice a day). After preoperative treatment, total mesorectal excision was performed 2-4 weeks in the TNT group and 6-10 weeks in the CRT group, followed by optional additional adjuvant chemotherapy. The primary endpoint is the pCR rate, and secondary endpoints include disease-related treatment failure, quality of life, and cost-effectiveness. Assuming a pCR rate of 28% and 15% in the TNT and CRT groups, respectively, and one-side alpha error rate of 0.025 and power of 80%, 348 patients will be enrolled considering 10% dropout rate. DISCUSSION: The TV-LARK trial will evaluate the superiority of employed TNT regimen against the standard CRT regimen for patients with LARC. We aimed to identify a TNT regimen that will improve the pCR rate and decrease systemic recurrence in these patients. TRIAL REGISTRATION: Cris.nih.go.kr ID: KCT0007169 (April 08, 2022). The posted information will be updated as needed to reflect the protocol amendments and study progress.

Current Status and Key Issues of Data Management in Tertiary Hospitals: A Case Study of Seoul National University Hospital.

OBJECTIVES: In the era of the Fourth Industrial Revolution, where an ecosystem is being developed to enhance the quality of healthcare services by applying information and communication technologies, systematic and sustainable data management is essential for medical institutions. In this study, we assessed the data management status and emerging concerns of three medical institutions, while also examining future directions for seamless data management. METHODS: To evaluate the data management status, we examined data types, capacities, infrastructure, backup methods, and related organizations. We also discussed challenges, such as resource and infrastructure issues, problems related to government regulations, and considerations for future data management. RESULTS: Hospitals are grappling with the increasing data storage space and a shortage of management personnel due to costs and project termination, which necessitates countermeasures and support. Data management regulations on the destruction or maintenance of medical records are needed, and institutional consideration for secondary utilization such as long-term treatment or research is required. Government-level guidelines for facilitating hospital data sharing and mobile patient services should be developed. Additionally, hospital executives at the organizational level need to make efforts to facilitate the clinical validation of artificial intelligence software. CONCLUSIONS: This analysis of the current status and emerging issues of data management reveals potential solutions and sets the stage for future organizational and policy directions. If medical big data is systematically managed, accumulated over time, and strategically monetized, it has the potential to create new value.

Plasma Circulating Cell-free DNA in Advanced Hepatocellular Carcinoma Patients Treated With Radiation Therapy.

BACKGROUND/AIM: Although radiation therapy (RT) is an effective and safe treatment when administered locally for various stages of hepatocellular carcinoma (HCC), adequate biomarkers that are predictive of therapeutic efficacy have not been identified. We evaluated the clinical utility of circulating cell-free DNA (cfDNA) to predict treatment response of patients with HCC treated with RT. PATIENTS AND METHODS: We prospectively recruited 37 patients diagnosed with HCC between March 2019 and May 2020. All patients were treated with RT as salvage therapy. Whole peripheral blood was collected twice, one before RT (baseline; V1) and another aliquot one week after the end of RT (V2). We determined whether cfDNA genomic copy number variations (CNVs) could predict treatment outcome. An I-score was calculated from the plasma cfDNA that reflected CNVs of cfDNA, which is evidence of genomic instability. RESULTS: The I-score at V1 exhibited a strong correlation with the planning target volume (PTV) (coefficient=0.65) and was a predictive marker for progression-free survival (PFS). In particular, a mean I-score value at V1 of ≥6.3 had a significant positive correlation with PFS (p=0.017). Compared with patients who had a complete response (CR) following RT, non-CR patients had a higher mean I-score value at V2 ≥6.2 (p=0.034). Furthermore, I-score values at V1 and V2 and the delta I-score ratio were significantly associated with a pre-RT alpha-fetoprotein level ≥200 among non-CR patients. CONCLUSION: I-score values calculated from plasma cfDNA represent a potential biomarker for predicting treatment outcomes in patients with advanced HCC receiving RT.

Differential Perspectives by Specialty on Oligometastatic Colorectal Cancer: A Korean Oligometastasis Working Group's Comparative Survey Study.

PURPOSE: Despite numerous studies on the optimal treatments for oligometastatic disease (OMD), there is no established interdisciplinary consensus on its diagnosis or classification. This survey-based study aimed to analyze the differential opinions of colorectal surgeons and radiation oncologists regarding the definition and treatment of OMD from the colorectal primary. MATERIALS AND METHODS: A total of 141 participants were included in this study, consisting of 63 radiation oncologists (44.7%) and 78 colorectal surgeons (55.3%). The survey consisted of 19 questions related to OMD, and the responses were analyzed using the chi-square test to determine statistical differences between the specialties. RESULTS: The radiation oncologists chose "bone" more frequently compared to the colorectal surgeons (19.2% vs. 36.5%, p=0.022), while colorectal surgeons favored "peritoneal seeding" (26.9% vs. 9.5%, p=0.009). Regarding the number of metastatic tumors, 48.3% of colorectal surgeons responded that "irrelevant, if all metastatic lesions are amendable to local therapy", while only 21.8% of radiation oncologist chose same answer. When asked about molecular diagnosis, most surgeons (74.8%) said it was important, but only 35.8% of radiation oncologists agreed. CONCLUSION: This study demonstrates that although radiation oncologists and colorectal surgeons agreed on a majority of aspects such as diagnostic imaging, biomarker, systemic therapy, and optimal timing of OMD, they also had quite different perspectives on several aspects of OMD. Understanding these differences is crucial to achieving multidisciplinary consensus on the definition and optimal management of OMD.

Genomic landscape of locally advanced rectal adenocarcinoma: Comparison between before and after neoadjuvant chemoradiation and effects of genetic biomarkers on clinical outcomes and tumor response.

PURPOSE: To explore genomic biomarkers in rectal cancer by performing whole-exome sequencing. MATERIALS AND METHODS: Pre-chemoradiation (CRT) biopsy and post-CRT surgical specimens were obtained from 27 patients undergoing neoadjuvant CRT followed by definitive resection. Exomes were sequenced to a mean coverage of 30×. Somatic single-nucleotide variants (SNVs) and insertions/deletions (indels) were identified. Tumor mutational burden was defined as the number of SNVs or indels. Mutational signatures were extracted and fitted to COSMIC reference signatures. Tumor heterogeneity was quantified with a mutant-allele tumor heterogeneity (MATH) score. Genetic biomarkers and frequently occurred copy number alterations (CNAs) were compared between pre- and post-CRT specimens. Their associations with tumor regression grade (TRG) and clinical outcomes were explored. RESULTS: Top five mutated genes were APC, TP53, NF1, KRAS, and NOTCH1 for pre-CRT samples and APC, TP53, NF1, CREBBP, and ATM for post-CRT samples. Several gene mutations including RUNX1, EGFR, and TP53 in pre-CRT samples showed significant association with clinical outcomes, but not with TRG. However, no such association was found in post-CRT samples. Discordance of driver mutation status was found between pre- and post-CRT samples. In tumor mutational burden analysis, higher number of SNVs or indels was associated with worse treatment outcomes. Six single-base substitution (SBS) signatures identified were SBS1, SBS30, SBS29, SBS49, SBS3, and SBS44. The MATH score decreased after CRT on paired analysis. Less than half of CNAs frequent in post-CRT samples were present in pre-CRT samples. CONCLUSION: Pre- and post-CRT samples showed different genomic landscape. Potential genetic biomarkers of pre-CRT samples found in the current analysis call for external validation.

Trajectories of Anxiety Symptoms for COVID-19 Patients Using Multimodal Data Collected from Telemedicine.

We designed and developed Remote Patient Monitoring (RPM) system specific for coronavirus (COVID-19) patients, and collected multimodal data. Using the collected data, we explored the trajectories of anxiety symptoms for 199 COVID-19 patients quarantined at home. Two classes were identified using latent class linear mixed model. Thirty-six patients showed an exacerbation of anxiety. Presence of initial psychological symptoms, pain on the start day of quarantine, and abdominal discomfort at one month after finishing the quarantine were associated with exacerbation of anxiety.

Posttransplant sequential adrenal and spine metastasis of hepatocellular carcinoma responsive to combined regorafenib and radiotherapy: a case report.

Adrenal and spinal metastases of hepatocellular carcinoma (HCC) are rare entities with significant morbidity and mortality, particularly after liver transplantation (LT). We report a case of a 49-year-old man who underwent LT for hepatitis B-related end-stage liver disease and HCC (single 4.5 cm lesion [T1N0], without vascular invasion) in 2016. Eighteen months later, adrenal metastasis and hepatitis B seropositive conversion were developed with normal serum tumor. Adrenal metastasis was treated with radiation therapy (RT) and hepatitis B showed spontaneous seronegative conversion. However, 35 months later, spinal metastasis occurred with elevation of the protein induced by vitamin K absence or antagonist-II (PIVKA-II) level (197 mAU/mL), along with hepatitis B seropositive conversion. After sorafenib, sequential regorafenib with RT led to partial response of the spinal lesions, along with hepatitis B seronegative conversion and normal PIVKA-II levels. After 9 months of regorafenib combined with RT, two recurrent lesions were found, as well as hepatitis B seropositive conversion and lesions were treated with transarterial chemoembolization. The patient survived for more than 71 months after LT and 53 months after recurrence under various combinations of therapy. Combined systemic and locoregional therapies can be a treatment option for HCC recurrence, even in LT patients.

Integrative modeling of tumor genomes and epigenomes for enhanced cancer diagnosis by cell-free DNA.

Multi-cancer early detection remains a key challenge in cell-free DNA (cfDNA)-based liquid biopsy. Here, we perform cfDNA whole-genome sequencing to generate two test datasets covering 2125 patient samples of 9 cancer types and 1241 normal control samples, and also a reference dataset for background variant filtering based on 20,529 low-depth healthy samples. An external cfDNA dataset consisting of 208 cancer and 214 normal control samples is used for additional evaluation. Accuracy for cancer detection and tissue-of-origin localization is achieved using our algorithm, which incorporates cancer type-specific profiles of mutation distribution and chromatin organization in tumor tissues as model references. Our integrative model detects early-stage cancers, including those of pancreatic origin, with high sensitivity that is comparable to that of late-stage detection. Model interpretation reveals the contribution of cancer type-specific genomic and epigenomic features. Our methodologies may lay the groundwork for accurate cfDNA-based cancer diagnosis, especially at early stages.

One-Week versus Two-Week Chemoradiotherapy Followed by Curative Surgery in Rectal Cancer: Long-Term Comparative Pooled Analysis of Two Prospective Multicenter Phase II Trials.

PURPOSE: The optimal short-course chemotherapeutic regimen for rectal cancer has not been clearly defined until now. KROG 10-01 and KROG 11-02 prospective trials investigated the efficacy and safety of 1- and 2-week chemoradiotherapy (CRT), respectively. Materials and Methods: Patients eligible for KROG 10-01 and KROG 11-02 involved those with clinical T3-4N0-2M0 rectal cancers. They received preoperative CRT and total mesorectal excision. Patients in KROG 10-01 received radiation of 25 Gy in 5 fractions during 1 week with 5-fluorouracil/leucovorin. Patients in KROG 11-02 received radiation of 33 Gy in 10 fractions for 2 weeks with oral capecitabine. RESULTS: A total of 150 patients consisting of 70 patients from KROG 10-01 and 80 patients from KROG 11-02 were collectively analyzed. With a median follow-up time of 89.2 months, the 5-year overall survival rate was 86.5% in 1-week CRT and 85.3% in 2-week CRT (p=0.841). The 5-year recurrence-free survival rate was 83.5% in 1-week CRT and 77.1% in 2-week CRT (p=0.448). One patient (1.4%) in 1-week CRT and 11 patients (13.8%) in 2-week CRT exhibited pathologic complete regression (ypT0N0M0) after radiotherapy (p=0.006). One-week CRT had significantly higher acute hematologic (12.8% vs. 3.8%, p=0.040) and nonhematologic (38.6% vs. 16.3%, p=0.002) toxicity than 2-week CRT. CONCLUSION: Both 1- and 2-week schedules of CRT showed favorable survival outcomes after 7 years of follow-up. But, 2-week course achieved more increased tumor response and decreased acute toxicity than 1-week course.

Metastasis-Directed Local Therapy of Hepatic Oligometastasis from Colorectal Cancer and Future Perspective in Radiation Therapy.

Introduction of the concept for oligometastasis led to wide application of metastasis-directed local ablative therapies for metastatic colorectal cancer (CRC). By application of the metastasis-directed local ablative therapies including surgical resection, radiofrequency ablation (RFA), and stereotactic ablative body radiotherapy (SABR), the survival outcomes of patients with metastatic CRC have improved. The liver is the most common distant metastatic site in CRC patients, and recently various metastasis-directed local therapies for hepatic oligometastasis from CRC (HOCRC) are widely used. Surgical resection is the first line of metastatic-directed local therapy for HOCRC, but its eligibility is very limited. Alternatively, RFA can be applied to patients who are ineligible for surgical resection of liver metastasis. However, there are some limitations such as inferior local control (LC) compared with surgical resection and technical feasibility based on location, size, and visibility on ultrasonography of the liver metastasis. Recent advances in radiation therapy technology have led to an increase in the use of SABR for liver tumors. SABR is considered complementary to RFA for patients with HOCRC who are ineligible for RFA. Furthermore, SABR can potentially result in better LC for liver metastases > 2-3 cm compared with RFA. In this article, the previous studies regarding curative metastasis-directed local therapies for HOCRC based on the radiation oncologist's and surgeon's perspective are reviewed and discussed. In addition, future perspectives regarding SABR in the treatment of HOCRC are suggested.