Whole-Genome Sequencing Reveals Mutational Signatures Related to Radiation-Induced Sarcomas and DNA-Damage-Repair Pathways.

Radiation-induced sarcoma (RIS) is a rare but serious late complication arising from radiotherapy. Despite unfavorable clinical outcomes, the genomic footprints of ionizing radiation in RIS development remain largely unknown. Hence, this study aimed to characterize RIS genomes and the genomic alterations in them. We analyzed whole-genome sequencing in 11 RIS genomes matched with normal genomes to identify somatic alterations potentially associated with RIS development. Furthermore, the abundance of mutations, mutation signatures, and structural variants in RIS were compared with those in radiation-naïve spontaneous sarcomas. The mutation abundance in RIS genomes, including one hypermutated genome, was variable. Cancer-related genes might show different types of genomic alterations. For instance, NF1, NF2, NOTCH1, NOTCH2, PIK3CA, RB1, and TP53 showed singleton somatic mutations; MYC, CDKN2A, RB1, and NF1 showed recurrent copy number alterations; and NF2, ARID1B, and RAD51B showed recurrent structural variations. The genomic footprints of nonhomologous end joining are prevalent at indels of RIS genomes compared with those in spontaneous sarcoma genomes, representing the genomic hallmark of RIS genomes. In addition, frequent chromothripsis was identified along with predisposing germline variants in the DNA-damage-repair pathways in RIS genomes. The characterization of RIS genomes on a whole-genome sequencing scale highlighted that the nonhomologous end joining pathway was associated with tumorigenesis, and it might pave the way for the development of advanced diagnostic and therapeutic strategies for RIS.

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.

Role of radiotherapy in Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma treated with sorafenib.

BACKGROUND AND AIM: This study aimed to investigate the clinical benefits of locoregional radiation therapy (RT) before, after, and concurrent with sorafenib therapy for Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) patients. METHODS: Patients treated with sorafenib for BCLC stage C HCC between January 2015 and December 2017 were retrospectively reviewed. In this study, only RT to locoregional sites, including the primary HCC, tumor thrombosis, or lymph node metastasis, was analyzed. Propensity score matching was used to adjust important baseline characteristics between groups. RESULTS: Among 398 patients treated with sorafenib, 68 (17.1%) patients were treated with locoregional RT. Median progression-free survival and overall survival (OS) were 2.2 and 9.5 months, respectively. In the multivariate analysis, locoregional RT (P < 0.001) was associated with a favorable OS. After 1:1 propensity score matching, patients who did not receive locoregional RT showed a worse OS than those who received RT (median 9.6 vs 15.7 months, P = 0.017). Whereas locoregional RT before/concurrent with sorafenib did not result in prolonged OS, locoregional RT after sorafenib showed significantly prolonged OS compared with sorafenib without locoregional RT (P = 0.003). Moreover, patients treated with ≥ 12 weeks of sorafenib significantly benefited from locoregional RT (15.3 vs 23.6 months, P = 0.046). CONCLUSION: Locoregional RT was associated with significantly longer survival in BCLC stage C HCC patients who were treated with sorafenib. Therefore, incorporating locoregional RT could improve the dismal prognosis for these patients.

Potential intrinsic subtype dependence on the association between metformin use and survival in surgically resected breast cancer: a Korean national population-based study.

PURPOSE: Numerous studies have suggested that metformin treatment can increase breast cancer survival; however, it is unclear whether its effects interact with intrinsic subtype or diabetic status. Therefore, we conducted a large nationwide study to assess this in women with surgically resected invasive breast cancer. METHODS: Patients with newly diagnosed breast cancer between 2007 and 2016 were identified using the national health insurance claims database of South Korea. Metformin or other drug exposures was defined as medication for ≥ 90 days. Breast cancer subtypes were classified into four groups based on hormonal therapy and anti-HER2 treatments. RESULTS: A total of 117,333 patients were included (median follow-up duration, 90 months). Type 2 diabetes mellitus (T2DM) affected significantly overall survival (OS, 7 years, 89.7% vs. 92.4%, p < 0.001). A significant interaction was found between the use of metformin and insulin in patients with T2DM (p = 0.018). Thus, the subsequent analysis was limited to these patients and propensity score matching was performed. We found significantly increased OS in patients treated with metformin (7-year OS, 88.3% vs. 85.6%, p < 0.001). Interestingly, a significant effect was observed in the hormonal therapy (HT)+/HER2-targeted therapy (Tx)- group (p < 0.001), whereas no specific association was observed in the HT-/HER2 Tx- group (p = 0.220). CONCLUSIONS: Metformin administration may be associated with reduced mortality in patients with surgically resected breast cancer, particularly in the HT+/HER2 Tx- group. Clinical trials investigating metformin as a combination agent in breast cancer should stratify patients by curative resection, intrinsic subtype, the presence of T2DM, and the use of insulin.

Clinical significance of radiation dose-volume parameters and functional status on the patient-reported quality of life changes after thoracic radiotherapy for lung cancer: a prospective study.

PURPOSE: To date, limited data exist about the relationship between radiation dose-volume parameters and patient-reported quality of life (QOL) after thoracic radiotherapy (RT) for lung cancer. We conducted this prospective study to investigate which clinico-dosimetric factors have an impact on functional declines and symptom developments after thoracic RT for lung cancer. MATERIALS AND METHODS: The study included 44 patients who had underwent thoracic three-dimensional conformal RT at our institution from 2016 to 2017. The health-related QOL was assessed using the EORTC QLQ-C30 and QLQ-LC13 questionnaires before RT (preRT), at the end of RT (endRT), and 3, 6, and 12 months after the completion of RT. RT dose-volume parameters of adjacent normal organs such as the lung, heart, and esophagus were retrieved and used for regression analysis. RESULTS: Thoracic RT induced a temporary deterioration of many of the functional statuses and symptoms, but most of those improved and recovered to baseline levels 3 months after RT. However, the role function (RF) decline persisted until 6 months after RT (p < 0.05). Dysphagia showed the most noticeable change at the endRT (p < 0.001). In the multiple regression analysis, the absolute volume of body received at least 50 Gy (p = 0.021) and a preRT RF score (p = 0.001) was significantly associated with the endRT RF scores. Dysphagia at the endRT was significantly associated with the V40 of the esophagus (p = 0.047), preRT emotional function (p = 0.029), and receipt of concurrent chemotherapy (p = 0.022). CONCLUSIONS: Both the dosimetric parameters and preRT functional status have an impact on the weak aspect of patient-reported QOL, which may cause poor treatment compliance during and after thoracic RT. For patients with a low preRT QOL score or those having large tumor which may result in higher dose volumes, careful RT planning could prevent the deterioration of QOL after RT.

Long-term prognostic effect of hormone receptor subtype on breast cancer.

PURPOSE: To determine the long-term prognostic role of hormone receptor subtype in breast cancer using surveillance, epidemiology, and end results (SEER) database. METHODS: Data of 810,587 female operable invasive breast cancer patients from SEER database with a mean follow-up period of 94.2 months (range, 0-311 months) were analyzed. Hormone receptor subtype was classified into four groups based on estrogen receptor (ER) and progesterone receptor (PR) statuses: ER(+)/PR(+), ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-). RESULTS: Numbers of subjects with ER(+)/PR(+), ER(+)/PR(-), ER(-)/PR(+), ER(-)/PR(-), and unknown were 496,279 (61.2%), 86,858 (10.7%), 11,545 (1.4%), 135,441 (16.7%), and 80,464 (9.9%), respectively. The ER(+)/PR(+) subtype showed the best breast-cancer-specific survival, followed by ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-) subtypes in the respective order (all p < 0.001). Survival difference among hormone receptor subtypes was maintained in subgroup analysis according to anatomic stage, race, age group, and year of diagnosis. Hormone receptor subtype was a significant independent prognostic factor in multivariable analyses (p < 0.001). Hazard ratios of ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-) for breast-cancer-specific mortality risk were 1.419 (95% confidence interval [CI] 1.383-1.456), 1.630 (95% CI 1.537-1.729), and 1.811 (95% CI 1.773-1.848), respectively, with ER(+)/PR(+) as reference. CONCLUSION: Hormone receptor subtype is a significant independent prognostic factor in female operable invasive breast cancer patients with long-term effect. The ER(+)/PR(+) subtype shows the most favorable prognosis, followed by ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-) subtypes in the respective order. Prognostic impacts of hormone receptor subtypes are also maintained in subgroup analysis according to anatomic stage, race, age, and year of diagnosis.

Survival benefit of postoperative radiotherapy for ductal carcinoma in situ after breast-conserving surgery: a Korean population-based cohort study.

PURPOSE: It has been accepted that radiation therapy (RT) for ductal carcinoma in situ (DCIS) has no survival benefit despite increasing local control. However, a recent large database study reported a small but significant benefit. Using a Korean population-based large database, we examined the survival benefit of RT for DCIS after breast-conserving surgery (BCS) and analyzed which subgroup might derive benefit from it. METHODS: Data from 6038 female DCIS patients who underwent BCS with or without RT between 1993 and 2012 were included in this study. We used propensity score analysis to control for differences in baseline characteristics. RESULTS: Before adjusting, patients who received RT were more likely to have a large-sized tumor, poor histologic grade, poor nuclear grade, and less hormone receptor positivity. Ten-year overall survival (OS) rates were 95.0% in the non-RT group and 97.1% in the RT group (p < 0.001). After adjusting, previously noted differences of characteristics were substantially reduced, and then ten-year OS rates were 94.3% in the non-RT group and 97.6% in the RT group (p = 0.001). When examining the benefit of RT according to proposed prognostic scores, patients with a score of 0 showed no difference in OS by adding RT after BCS, whereas those with high scores demonstrated a significant benefit. CONCLUSIONS: We demonstrated the significant OS benefit of postoperative RT after BCS based on a large database, and for the first time beyond the western population. The omission of RT for selected patients to prevent overtreatment needs to be more elaborately studied.

Adjuvant Chemoradiotherapy is Associated with Improved Survival for Patients with Resected Gallbladder Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: The impact of adjuvant radiotherapy (ART) on survival from gallbladder carcinoma (GBC) remains underexplored, with conflicting results reported. A systematic review and meta-analysis was performed to clarify the impact of ART in GBC. METHODS: A systematic literature search of several databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, from inception to August 2016. Studies that reported survival outcomes for patients with or without ART after curative surgery were included. RESULTS: All the inclusion criteria was met by 14 retrospective studies including 9364 analyzable patients, but most of the studies had a moderate risk of bias. Generally, the ART group had more patients with unfavorable characteristics than the group that had surgery alone. Nevertheless, the pooled results showed that ART significantly reduced the risk of death (hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.44-0.67; p < 0.001) and recurrence (HR 0.61; 95% CI 0.38-0.98; p = 0.04) of GBC compared with surgery alone. Exploratory analyses demonstrated a survival benefit from ART for a subgroup of patients with lymph node-positive diseases (HR 0.61; p < 0.001) and R1 resections (HR 0.55; p < 0.001), but not for patients with lymph node-negative disease (HR 1.06; p = 0.78). No evidence of publication bias was found (p = 0.663). CONCLUSIONS: This study is the first meta-analysis to evaluate the role of ART and to provide supporting evidence that ART may offer survival benefits, especially for high-risk patients. However, further confirmation with a randomized prospective study is needed to clarify the subgroup of GBC patients who would benefit most from ART.

The impact of perioperative CA19-9 change on the survival and recurrence patterns after adjuvant chemoradiotherapy in resectable extrahepatic cholangiocarcinoma.

BACKGROUNDS: Perioperative CA19-9 value in pancreato-biliary cancers has been recognized as a prognostic factor. Herein, we investigated survival differences and recurrence patterns after adjuvant chemoradiotherapy by perioperative CA19-9 change in surgically resected extrahepatic cholangiocarcinoma. METHODS: Patients were divided into those with preoperative normal CA19-9 (Group 1, n = 52), those with high preoperative and normalized postoperative CA19-9 (Group 2, n = 80), and those with both high pre- and postoperative CA19-9 (Group 3, n = 21). RESULTS: Depending on the group defined above, the 5-year overall survival (OS) (59.6%, 38.7%, and 9.5%, P < 0.001) and disease-free survival (55.8%, 31.2%, and 9.5%, P < 0.001) between the three groups differed. On multivariable analysis in patients other than group 1, poor prognosticators for OS were high postoperative CA19-9 (HR 2.26, P = 0.008) and N1 disease (HR 2.33, P = 0.001). Group 3, compared with group 2, showed higher distant metastasis rate, shorter disease-free interval, and higher CA19-9 at the time of recurrence. CONCLUSIONS: Survival and recurrence patterns after adjuvant chemoradiotherapy are significantly affected by perioperative CA19-9 change. This may have important implications in patient selection for adjuvant chemoradiotherapy and clinical trial design.

Novel graded prognostic assessment for colorectal cancer patients with brain metastases.

PURPOSE: It is important to take into account potential prognostic factors to select patients with brain metastasis from colorectal cancer (CRC) who will benefit from active neurosurgical treatment. Therefore, we experimentally investigated our single institutional data to develop a novel CRC-specific graded prognostic assessment (GPA) and to help clinicians determine the optimal management. METHODS AND MATERIALS: We retrospectively reviewed the records of 107 patients with brain metastases from CRC who received any kind of treatment in our hospital and had sufficient clinical information. RESULTS: The median overall survival was 5.2 months, and the 1- and 2-year overall survival rates were 23.7 and 6.6%, respectively. Multivariate analysis revealed that the number of brain metastases ≥ 6, presence of neurologic symptoms, and elevated serum carcinoembryonic antigen (≥ 30 ng/ml) were the independent prognostic factors for poor overall survival, while performance status was not. Based on this, we developed the CRC-specific GPA index and stratified patients into three categories. The median overall survival for patients with GPA scores of 0-0.5, 1.0-1.5, and 2.0-2.5 was 2.3, 4.3, and 12.7 months, respectively (p < 0.001). Surgery or stereotactic radiosurgery ± whole-brain radiotherapy showed a better survival than palliative whole-brain radiotherapy alone in patients with high GPA scores. CONCLUSIONS: We developed a novel CRC-specific GPA index, which could help physicians to stratify patients with brain metastases. Further efforts are needed to validate and improve this index.

Clinical outcomes of stereotactic ablative radiotherapy in patients with pulmonary metastasis.

BACKGROUNDS: In addition to its curative use for early stage lung cancer, stereotactic ablative radiotherapy is also indicated for pulmonary metastatic disease. Aims of this study were to retrospectively analyze treatment outcomes and to find prognostic factors for survivals. METHODS: Treatment outcomes and toxicities of 85 cases of SABR in 72 patients were retrospectively reviewed from September 2012 to April 2015. Prognostic factors were analyzed using Cox proportional hazards regression. RESULTS: The local failure-free survival rate at 2 years was 98%. Of the case, 1-year and 2-year progression-free survival rates were 62% and 48%, and overall survival rates were 90% and 72%, respectively. Multivariate analyses demonstrated that controlled primary cancer (P = 0.01), absence of extra-pulmonary metastatic disease (P < 0.01) and disease-free interval longer than 1 year (P < 0.01) favorably affected progression-free survival. Furthermore, the absence of extra-pulmonary metastatic disease (P < 0.01) increased overall survival as well. Grade 1 or 2 radiation pneumonitis was found in 37 cases, and Grade 1 chest wall pain was found in 1 case. CONCLUSIONS: Stereotactic ablative radiotherapy demonstrated good local control with tolerable adverse effects for pulmonary metastasis. The presence or absence of extra-pulmonary metastasis was found to be prognostic factor of mortality after stereotactic ablative radiotherapy treatment.

Risk stratification and prognostic nomogram for post-recurrence overall survival in patients with recurrent extrahepatic cholangiocarcinoma.

BACKGROUND: This study aimed to investigate post-recurrence overall survival (PROS) in patients with recurrent extrahepatic cholangiocarcinoma (EHC) and to indicate which groups of patients need active salvage treatments. METHODS: We retrospectively reviewed the records of 251 consecutive patients who underwent curative surgery followed by adjuvant chemoradiotherapy for EHC. Among these, 144 patients experienced a recurrence and were included for further analysis. RESULTS: The median PROS was 7 months (range, 1-130). In multivariate analysis, poorly differentiated histology, short disease-free survival, poor performance status, and elevated CA 19-9 were identified as significant prognosticators for poor PROS. Based on this, we stratified study patients into three categories by the number of risk factors: group 1 (0 or 1 factors), group 2 (2 factors) and group 3 (3-4 factors). Median PROS for groups 1, 2, and 3 were 13, 7, and 5 months, respectively (p < 0.001). Group 1 patients showed a significant benefit from salvage treatment, but groups 2 and 3 did not demonstrate clear benefit. In addition, we developed a nomogram to specifically identify individual patient's prognosis. CONCLUSION: Our simple risk stratification as well as proposed nomogram can classify patients into subgroups with different prognosis and will help facilitate personalized strategies after recurrence.

Survival Benefit of Adjuvant Chemoradiotherapy in Patients With Ampulla of Vater Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis focusing on the impact of adjuvant radiotherapy (RT) on overall survival (OS) in ampulla of Vater (AoV) cancer. BACKGROUND: The adjuvant treatment for AoV cancer is a subject of controversy without convincing evidence from randomized study. METHODS: A comprehensive search was performed in the databases of EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to July 2014. We included studies, which compared survival between patients with or without adjuvant RT after curative surgery solely for AoV cancer. Hazard ratio (HR) for OS was extracted, and a random-effects model was used for pooled analysis. RESULTS: Ten retrospective studies including 3361 patients met all inclusion criteria and were included for the final meta-analysis. Adjuvant RT was delivered with concurrent chemotherapy, mostly 5-fluorouracil, in all institutional studies. Generally, adjuvant RT groups included more patients with locally advanced disease or lymph node metastasis than did the surgery alone groups. The pooled results demonstrated that adjuvant RT significantly reduced the risk of death (HR = 0.75; P = 0.01). Exploratory analyses showed that patients with lymph node metastasis (HR = 0.52; P = 0.001) and locally advanced disease (HR = 0.42; P = 0.001) may also have survival benefit from adjuvant RT. No clear evidence of publication bias was found. CONCLUSIONS: This is the first meta-analysis evaluating the role of adjuvant RT in AoV cancer. Our results suggest the potential for survival benefit of adjuvant chemoradiotherapy. Further studies, preferably randomized clinical trials, are needed to confirm our results.

Long-term toxicities after allogeneic hematopoietic stem cell transplantation with or without total body irradiation: a population-based study in Korea.

PURPOSE: To compare long-term toxicity incidences, including secondary cancer (SC) with or without total body irradiation (TBI), in Asian patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using a nationwide database. MATERIALS AND METHODS: We identified 4,554 patients receiving HSCT for leukemic disease from 2009 to 2016 using the healthcare bigdata system of Korea. Incidence rate ratios (IRRs) for SC, cataracts, hypothyroidism, chronic kidney disease (CKD), myocardial infarction, or strokes were compared, and standardized incidence ratios (SIR) of SC was also estimated. RESULTS: TBI was conducted on 1,409 patients (30.9%). No overall survival differences based on TBI were observed. With a median follow-up duration of 58.2 months, 143 patients were diagnosed with subsequent SC (3.4%). Incidence rates per 1,000 person-year were 6.56 (95% confidence interval [CI], 4.8-8.8) and 7.23 (95% CI, 5.9-8.8) in the TBI and no-TBI groups, respectively (p = 0.594). Also, the SIR (95% CI) was not significantly increased by TBI (1.32 [0.86-1.94] vs. 1.39 [1.08-1.77] in the no-TBI group). In the young age group (0-19 years), SIRs were increased in both groups regardless of TBI (8.60 vs. 11.96). The IRRs of cataracts (1.60; 95% CI, 1.3-2.0), CKD (1.85; 95% CI, 1.3-2.6), and hypothyroidism (1.50; 95% CI, 1.1-2.1) were significantly increased after TBI. However, there were no significant differences in the occurrence of myocardial infarction and stroke according to TBI. CONCLUSION: Our results suggest that modern TBI may not additionally increase the risk of SC after allogeneic HSCT, although increased risks of other diseases were noted. Physicians should carefully consider individualized risks and benefits of TBI, with a particular focus by age group.

Risk of clinically significant cardiovascular disease associated with postoperative radiotherapy in non-small cell lung cancer patients receiving surgical resection followed by adjuvant chemotherapy: A Korean nationwide cohort study.

BACKGROUND: There are no large-scale datasets that analyze the relationship between postoperative radiotherapy (PORT) and various cardiovascular diseases (CVDs) in patients with locally advanced non-small cell lung cancer (NSCLC). Therefore, we aimed to investigate the incidences of CVDs with PORT using a national population-based database. METHODS: Patients diagnosed with NSCLC who underwent curative surgery followed by adjuvant chemotherapy were included from 2007 to 2017. Patients with a prior diagnosis of heart failure (HF), atrial fibrillation (AFib), or heart surgery were excluded. A total of 11,141 patients were included in the final analysis. PORT was used in 1334 patients. Most patients received lobectomy with mediastinal lymph node dissection. RESULTS: Major adverse cardiac events mostly occurred within 3-4 years from the diagnosis. After the median follow-up duration of 70.6 months, HF was the most diagnosed disease (5.3 %), followed by AFib (4.5 %), stroke (4.1 %), and pulmonary embolism (3.5 %). All the incidences of clinically significant CVDs did not differ by PORT. This result remained unchanged after the propensity score matching comparison. Age ≥ 65, underlying hypertension, and history of ischemic heart disease were the most related factors to the occurrence of HF and AFib. No significant difference in CVD-free survivals according to PORT status was observed. When stratified by proposed scoring, there were no subgroups showed increased incidence by PORT. CONCLUSIONS: These results suggest that PORT had no significant impact on various CVD occurrences in NSCLC patients without underlying heart disease.

Intrathoracic Progression Is Still the Most Dominant Failure Pattern after First-Line Chemo-immunotherapy in Extensive-Stage Small-Cell Lung Cancer: Implications for Thoracic Radiotherapy.

PURPOSE: This study aimed to compare the failure patterns before and after the introduction of immunotherapy and to determine the role of thoracic radiotherapy (TRT) in extensive-stage small-cell lung cancer (ES-SCLC) treatment. MATERIALS AND METHODS: We retrospectively reviewed 294 patients with ES-SCLC, of which 62.2% underwent chemotherapy alone, 13.3% underwent chemotherapy followed by consolidative TRT (TRT group), and 24.5% underwent chemotherapy with immune checkpoint inhibitor (ICI group). We performed propensity-score matching (PSM) to compare each treatment group. RESULTS: The median follow-up duration was 10.4 months. At the first relapse, in the cohort showing objective response, the proportion of cases showing intrathoracic progression was significantly lower in the TRT group (37.8%) than in the chemotherapy-alone (77.2%, p < 0.001) and the ICI (60.3%, p=0.03) groups. Furthermore, in the subgroup analysis, TRT showed benefits related to intrathoracic progression-free survival (PFS) in comparison with ICI in patients with less than two involved extrathoracic sites (p=0.008) or without liver metastasis (p=0.02) or pleural metastasis (p=0.005) at diagnosis. After PSM, the TRT group showed significantly better intrathoracic PFS than both chemotherapy-alone and ICI groups (p < 0.001 and p=0.04, respectively), but showed no significant benefit in terms of PFS and overall survival in comparison with the ICI group (p=0.17 and p=0.31, respectively). CONCLUSION: In ES-SCLC, intrathoracic progression was the most dominant failure pattern after immunotherapy. In the era of chemoimmunotherapy, consolidative TRT can still be considered a useful treatment strategy for locoregional control.

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.

Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 1. Brain and head and neck.

Advances in radiotherapy (RT) techniques, including intensity-modulated RT and image-guided RT, have allowed hypofractionation, increasing the fraction size over the conventional dose of 1.8-2.0 Gy. Hypofractionation offers advantages such as shorter treatment times, improved compliance, and under specific conditions, particularly in tumors with a low α/ß ratio, higher efficacy. It was initially explored for use in RT for prostate cancer and adjuvant RT for breast cancer, and its application has been extended to various other malignancies. Hypofractionated RT (HFRT) may also be effective in patients who are unable to undergo conventional treatment owing to poor performance status, comorbidities, or old age. The treatment of brain tumors with HFRT is relatively common because brain stereotactic radiosurgery has been performed for over two decades. However, re-irradiation of recurrent lesions and treatment of elderly or frail patients are areas under investigation. HFRT for head and neck cancer has not been widely used because of concerns regarding late toxicity. Thus, we aimed to provide a comprehensive summary of the current evidence for HFRT for brain tumors and head and neck cancer and to offer practical recommendations to clinicians faced with the challenge of choosing new treatment options.

Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 2. Lung (non-small cell lung cancer).

Several recent studies have investigated the use of hypofractionated radiotherapy (HFRT) for various cancers. However, HFRT for non-small cell lung cancer (NSCLC) with or without concurrent chemotherapy is not yet widely used because of concerns about serious side effects and the lack of evidence for improved treatment results. Investigations of HFRT with concurrent chemotherapy in NSCLC have usually been performed in single-arm studies and with a small number of patients, so there are not yet sufficient data. Therefore, the Korean Society for Radiation Oncology Practice Guidelines Committee planned this review article to summarize the evidence on HFRT so far and provide it to radiation oncology clinicians. In summary, HFRT has demonstrated promising results, and the reviewed data support its feasibility and comparable efficacy for the treatment of locally advanced NSCLC. The incidence and severity of esophageal toxicity have been identified as major concerns, particularly when treating large fraction sizes. Strategies, such as esophagus-sparing techniques, image guidance, and dose constraints, may help mitigate this problem and improve treatment tolerability. Continued research and clinical trials are essential to refine treatment strategies, identify optimal patient selection criteria, and enhance therapeutic outcomes.

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.