Diagnostic assessments and treatment results of well-differentiated gastric-type adenocarcinoma of the uterine cervix (Adenoma malignum): A multicenter retrospective analysis of KROG 22-03 study.

OBJECTIVE: Among cervical adenocarcinomas, well-differentiated gastric adenocarcinoma of the uterine cervix (WD-GAS), previously termed adenoma malignum (minimal deviation adenocarcinoma) is not well understood. Because of its rarity and difficulty in diagnosis, there is no standard care for WD-GAS. Thus, we conducted the first multicenter retrospective study on WD-GAS to clarify prognostic factors for long-term survival and recurrence. METHODS: Patients diagnosed with WD-GAS at eight hospitals participated in this multi-center study. Overall survival (OS) and recurrence-free survival (RFS) were calculated with the Kaplan-Meier method. Additionally, OS between the early and advanced FIGO stage groups were compared with the log-rank test. Cox regression analysis was conducted to identify significant factors associated with recurrence-free survival (RFS). RESULTS: A total of 73 patients from eight hospitals in South Korea were included in the analysis. The median follow-up period was 44.8 months, and all patients underwent curative surgical intervention as the primary treatment. Recurrence was observed in 17 patients (23.3%). Ten patients had locoregional recurrence, four patients had distant metastasis, and three patients presented with both locoregional recurrence and distant metastasis. The Cox regression analysis identified several statistically significant factors associated with RFS, including vaginal invasion (VI), parametrial invasion (PMI), resection margin (RM), and nodal and lymphovascular invasion (LVI). When considering these five factors together, patients without any of the factors exhibited recurrence-free survival (RFS) of 97.0% at three years and those with more than one of these factors had a 3-year RFS of 65.4% (P < 0.001). CONCLUSION: WD-GAS showed relatively high locoregional recurrence rate. Positive PMI, VI, RM, nodal involvement, and LVI were associated with a significant increase in recurrence or distant metastasis rates.

Modulation of CD8+ T Cell Responses by Radiotherapy-Current Evidence and Rationale for Combination with Immune Checkpoint Inhibitors.

Radiotherapy for cancer has been known to affect the responses of immune cells, especially those of CD8+ T cells that play a pivotal role in anti-tumor immunity. Clinical success of immune checkpoint inhibitors led to an increasing interest in the ability of radiation to modulate CD8+ T cell responses. Recent studies that carefully analyzed CD8+ T cell responses following radiotherapy suggest the beneficial roles of radiotherapy on anti-tumor immunity. In addition, numerous clinical trials to evaluate the efficacy of combining radiotherapy with immune checkpoint inhibitors are currently undergoing. In this review, we summarize the current status of knowledge regarding the changes in CD8+ T cells following radiotherapy from various preclinical and clinical studies. Furthermore, key biological mechanisms that underlie such modulation, including both direct and indirect effects, are described. Lastly, we discuss the current evidence and essential considerations for harnessing radiotherapy as a combination partner for immune checkpoint inhibitors.

Evaluation of the dosimetric and radiobiological parameters in four radiotherapy regimens for synchronous bilateral breast cancer.

This study is to investigate the optimal treatment option for synchronous bilateral breast cancer (SBBC) by comparing dosimetric and radiobiological parameters of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans using single and dual isocenters. Twenty patients with SBBC without lymph node involvement were selected retrospectively. Four treatment plans were generated for each patient using the Eclipse treatment planning system (Varian Medical System, Palo Alto, CA, USA) following two delivery techniques with two isocenter conditions-IMRT using a single isocenter (IMRT_Iso1), VMAT using a single isocenter (VMAT_Iso1), IMRT using dual isocenters (IMRT_Iso2), and VMAT using dual isocenters (VMAT_Iso2). A dose of 42.56 Gy in 16 fractions was prescribed for the planning target volume (PTV). All plans were calculated using the Acuros XB algorithm and a photon optimizer for a 6-MV beam of a Vital Beam linear accelerator. PTV-related dosimetric parameters were analyzed. Further, the homogeneity index, conformity index, and conformation number were computed to evaluate plan quality. Dosimetric parameters were also measured for the organs at risk (OARs). In addition, the equivalent uniform dose corresponding to an equivalent dose related to a reference of 2 Gy per fraction, the tumor control probability, and the normal tissue complication probability were calculated based on the dose-volume histogram to investigate the radiobiological impact on PTV and OARs. IMRT_Iso1 exhibited similar target coverage and a certain degree of dosimetric improvement in OAR sparing compared to the other techniques. It also exhibited some radiobiological improvement, albeit insignificant. Although IMRT_Iso1 significantly increased monitor unit compared to VMAT_Iso1, which is the best option in terms of delivery efficiency, there was only a 22% increase in delivery time. Therefore, in conclusion, IMRT_Iso1, the complete treatment of which can be completed using a single setup, is the most effective method for treating SBBC.

A Phase II Study of Genexol-PM and Cisplatin as Induction Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma.

LESSONS LEARNED: Induction chemotherapy with Genexol-PM and cisplatin demonstrated modest tumor response in locally advanced head and neck squamous cell carcinoma.Considering favorable toxicity profiles and promising survival data, further studies on this regimen are warranted in patients with head and neck squamous cell carcinoma. BACKGROUND: Genexol-PM is a polymeric micellar formulation of paclitaxel without Cremophor EL. We investigated the efficacy and safety of Genexol-PM plus cisplatin as induction chemotherapy (IC) in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). METHODS: Patients received Genexol-PM (230 mg/m2) and cisplatin (60 mg/m2) every 3 weeks as IC. After three cycles of IC, definitive treatment of either concurrent chemoradiotherapy (CCRT) with weekly cisplatin (30 mg/m2) or surgery was performed. The primary endpoint was overall response rate (ORR) after IC. RESULTS: Of 52 patients enrolled, 47 completed three cycles of IC, and the ORR was 55.8% (95% confidence interval, 42.3-69.3). Although there was one treatment-related death, toxicity profiles to Genexol-PM and cisplatin were generally favorable, and the most common grade 3 or 4 toxicities were neutropenia (15.4%), anorexia (7.7%), and general weakness (7.7%). Fifty-one patients received definitive treatment (CCRT [n = 44] or radical surgery [n = 7]). The rate of complete response following CCRT was 81.8% (36/44). After a median follow-up of 39 months, estimates of progression-free survival (PFS) and overall survival (OS) at 3 years were 54.3% and 71.3%, respectively. CONCLUSION: IC with Genexol-PM and cisplatin demonstrated modest tumor response with well-tolerated toxicity profiles for patients with LA-HNSCC.

Tumor Boost Using External Beam Radiation in Cervical Cancer Patients Unable to Receive Intracavitary Brachytherapy: Outcome From a Multicenter Retrospective Study (Korean Radiation Oncology Group 1419).

PURPOSE: We conducted this study to evaluate the outcomes of external-beam radiotherapy tumor boost (EBRT-B) in cervical cancer patients who could not receive intracavitary brachytherapy. METHODS: A total of 11 hospitals provided the data of patients who received EBRT-B during the period from January 2005 through October 2012. RESULTS: A total of 75 patients were included. The median radiotherapy dose was 46 Gy (range, 40-54 Gy) for whole pelvis and 24 Gy (range, 9-35 Gy) for EBRT-B. Initial tumor responses assessed at 2 to 6 months after radiotherapy were as follows: 46 with complete response, 22 with partial response, 2 with stable disease, and 3 with progressive disease. After a median follow-up time of 33 months, 30 patients (40.0%) showed disease progression including 21 (28.0%) with local progression. The 5-year local failure-free survival rate was 70.0%. Achieving complete response at the first follow-up visit and an overall treatment time of 53 days or less were significantly related to favorable local failure-free survival. The rate of grade 3 or higher toxicity was 2.6%. CONCLUSIONS: Approximately 70% of patients had local tumor control after curative radiotherapy using EBRT-B. Early tumor response and overall treatment time of 53 days or less were closely associated with favorable local control.

Failure patterns according to molecular subtype in patients with invasive breast cancer following postoperative adjuvant radiotherapy: long-term outcomes in contemporary clinical practice.

PURPOSE: Although gene expression profiling provides critical information, knowledge remains limited regarding the differential effects of molecular subtype on clinical course. This study evaluated the impact of molecular status on long-term patterns of failure in patients with non-metastatic breast cancer. METHODS: We analyzed data from 1181 individuals with invasive breast cancer undergoing surgery plus PORT from 2003 to 2011. Molecular subtypes were defined as luminal A (LA), luminal B (LB)-HER2(-), LB-HER2(+), HER2, and triple-negative (TN) based on the 2013 St. Gallen Consensus criteria. Competing risks analysis and baseline hazard rate function plots were used to explore subtype-specific recurrence patterns. RESULTS: The 10-year overall survival rates of LA, LB-HER2(-), LB-HER2(+), HER2, and TN groups were 96, 93, 94, 84, and 85%, respectively (P < 0.001). Distant metastatic events differed significantly according to molecular subtype (P < 0.001). In competing risks regression analysis, initial development of distant metastasis was the highest with TN tumors, followed by HER2, LB-HER2(-), and LB-HER2(+) subtypes (P = 0.005). Regarding preferential sites of distant metastasis, the risk of initial brain metastasis was significantly higher with HER2 tumors, followed by TN tumors (P = 0.001). A low-level but sustained metastatic risk increment was observed in luminal tumors, whereas TN and HER2 subtypes showed a short-term risk surge within 5 years. CONCLUSION: From the significant impact of molecular profile on distant metastasis, subtype-specific individualization of systemic treatment and close surveillance are suggested. The preferential and long-term risk of brain metastasis in the HER2 subtype underlines the importance of alternative anti-HER2 therapies.

Magnetic resonance imaging during definitive chemoradiotherapy can predict tumor recurrence and patient survival in locally advanced cervical cancer: A multi-institutional retrospective analysis of KROG 16-01.

OBJECTIVE: Definitive chemoradiotherapy (CRT) followed by brachytherapy is a standard treatment for locally advanced cervical cancer. During CRT, marked reduction of cervical tumor is often observed in magnetic resonance imaging (MRI). The primary aim of this study was to assess the association between tumor response in MRI using FIGO classification and clinical outcomes. METHODS: Multi-institutional data were retrospectively reviewed to identify the significance of MR tumor response on tumor recurrence and patient survival. 225 patients with histologically confirmed squamous cell carcinoma of the cervix, staged as FIGO Ib2-IVa on initial pelvic MRI, were included. Post-CRT MRI was performed median 35days after the beginning of CRT and before brachytherapy. A median 54Gy of external radiation was given with weekly cisplatin during CRT. RESULTS: 112 (49.7%) of the 225 patients showed a positive response in post-CRT MRI and were named the responsive arm. After a median follow-up time of 36.2months, the responsive arm had significantly lower para-aortic recurrence (7.5% vs. 12.4%; p=0.04) and distant metastasis (13.2% vs. 27.6%; p=0.03) rates than did the non-responsive arm. The responsive arm had significantly higher 3-year cause-specific survival rate (94.6% vs. 81.1%, p<0.01) than did the non-responsive arm. In the multivariate analysis, tumor size (hazard ratio, 1.91 and 95% confidence interval, 1.07-3.43; p=0.028) and positive MR response (hazard ratio, 1.75 and 95% confidence interval, 1.06-2.27; p=0.045) were significant factors for recurrence-free survival CONCLUSION: Early tumor response evaluation with MRI using FIGO classification effectively predicted distant tumor metastasis and disease-specific survival in locally advanced cervical cancer.

Tumour size, volume, and marker expression during radiation therapy can predict survival of cervical cancer patients: a multi-institutional retrospective analysis of KROG 16-01.

OBJECTIVE: The aim of this multi-institutional study was to determine the prognostic impact of tumour parameters, such as tumour size (TS), tumour volume (TV), and marker expression, on survival during radiation therapy (RT) for cervical cancer patients. METHODS: A total of 231 patients with histologically confirmed cervical cancer, classified as Federation of Gynecology and Obstetrics (FIGO) Ib2-IVa, were enrolled in this study. Pre- and mid-RT pelvic magnetic resonance imaging (MRI) and squamous cell carcinoma antigen (SCC-ag) analysis were performed twice, during RT and just before brachytherapy. RESULTS: The median follow-up time was 27.8months (range, 2-116months). Multivariate analysis revealed that stage (odds ratio [OR], 2.936 and 95% confidence interval [CI], 1.119-7.707; P=0.029), tumour volume reduction rate (TVRR) (OR, 3.435 and 95% CI, 1.062-11.106; P=0.039), and SCC-ag reduction rate (SCCRR) (OR, 5.104 and 95% CI, 1.769-14.727; P=0.003) were independently associated with overall survival (OS), while pre-RT TS (OR, 2.148 and 95% CI, 1.221-3.810; P=0.009), mid-RT TV (OR, 3.106 and 95% CI, 1.685-5.724; P<0.0001) and SCCRR (OR, 1.954 and 95% CI, 1.133-3.369; P=0.016) were associated with progression-free survival (PFS). Based on the prognostic factor analysis, patients with the highest prognostic risk score of 3 showed poorer overall survival and progression free survival than patients with lower prognostic risk scores. CONCLUSION: We identified that tumour parameters such as TVRR, SCCRR, pre-RT TS, and mid-RT TV areindependent and strong prognostic parameters for patients with cervical cancer receiving RT. This scoring system-based prognostic factor analysis could be used to help develop optimized treatment plans for cervical cancer patients during RT.

Oncologic Outcomes After Adjuvant Radiotherapy for Stage II Endometrial Carcinoma: A Korean Radiation Oncology Group Study (KROG 14-10).

OBJECTIVE: The aim of this study was to investigate the survival, patterns of failure, and prognostic factors in patients with stage II endometrial carcinoma treated with adjuvant radiotherapy. METHODS: We reviewed the medical records of patients who underwent total hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection followed by adjuvant radiotherapy in 10 participating hospitals of the Korean Radiation Oncology Group. Most patients received adjuvant external beam radiation therapy, with a median dose of 50.4 Gy; approximately 50% of these patients received an additional brachytherapy boost, with a median dose of 18 Gy. Adjuvant chemotherapy was administered to 19 patients. RESULTS: A total of 122 patients were examined. Over a median follow-up period of 62.7 months (range, 1.9-158.8 months), the 5-year overall survival (OS) and disease-free survival rates were found to be 91.1% and 85.1%, respectively. Recurrence was observed in 14 patients (11.5%), including 3 with local recurrence and 11 with distant metastases as the first site of recurrence. Univariate analysis indicated that lymphovascular invasion was related to an unfavorable OS. An age of 60 years or above, histologic grade 3, and lymphovascular invasion were identified as risk factors for OS. Because there were several risk factors related to OS, we assigned patients to a high-risk group (defined as cases with ≥1 risk factors) and a low-risk group. The 5-year OS rate of the high-risk group was significantly inferior to that of the low-risk group (82.9% vs 100%, P = 0.003). CONCLUSIONS: The high-risk group had a significantly poorer survival rate than the low-risk group, and distant metastasis was the main pattern of recurrence, thus indicating that further adjuvant chemotherapy should be considered in high-risk patients.

Optimal planning strategy among various arc arrangements for prostate stereotactic body radiotherapy with volumetric modulated arc therapy technique.

BACKGROUND: The aim of this study was to determine the optimal strategy among various arc arrangements in prostate plans of stereotactic body radiotherapy with volumetric modulated arc therapy (SBRT-VMAT). PATIENTS AND METHODS: To investigate how arc arrangements affect dosimetric and biological metrics, SBRT-VMAT plans for eighteen patients were generated with arrangements of single-full arc (1FA), single-partial arc (1PA), double-full arc (2FA), and double-partial arc (2PA). All plans were calculated by the Acuros XB calculation algorithm. Dosimetric and radiobiological metrics for target volumes and organs at risk (OARs) were evaluated from dosevolume histograms. RESULTS: All plans were highly conformal (CI<1.05, CN=0.91) and homogeneous (HI=0.09-0.12) for target volumes. For OARs, there was no difference in the bladder dose, while there was a significant difference in the rectum and both femoral head doses. Plans using 1PA and 2PA showed a strong reduction to the mean rectum dose compared to plans using 1FA and 2FA. Contrastively, the D2% and mean dose in both femoral heads were always lower in plans using 1FA and 2FA. The average tumor control probability and normal tissue complication probability were comparable in plans using all arc arrangements. CONCLUSIONS: The use of 1PA had a more effective delivery time and produced equivalent target coverage with better rectal sparing, although all plans using four arc arrangements showed generally similar for dosimetric and biological metrics. However, the D2% and mean dose in femoral heads increased slightly and remained within the tolerance. Therefore, this study suggests that the use of 1PA is an attractive choice for delivering prostate SBRT-VMAT.

Inclined head position improves dose distribution during hippocampal-sparing whole brain radiotherapy using VMAT.

PURPOSE: Hippocampal-sparing whole brain radiotherapy (HS-WBRT) aims to preserve neurocognitive functions in patients undergoing brain radiotherapy (RT). Volumetric modulated arc therapy (VMAT) involves intensity-modulated RT using a coplanar arc. An inclined head position might improve dose distribution during HS-WBRT using VMAT. MATERIALS AND METHODS: This study analyzed 8 patients receiving brain RT with inclined head positioning. A comparable set of CT images simulating a non-inclined head position was obtained by rotating the original CT set. HS-WBRT plans of coplanar VMAT for each CT set were generated with a prescribed dose of 30 Gy in 10 fractions. Maximum dose to the hippocampi was limited to 16 Gy; to the optic nerve, optic chiasm, and eyeballs this was confined to less than 37.5 Gy; for the lenses to 8 Gy. Dosimetric parameters of the two different plans of 8 patients were compared with paired t-test. RESULTS: Mean inclined head angle was 11.09 ± 0.73°. The homogeneity (HI) and conformity (CI) indexes demonstrated improved results, with an average 8.4 ± 10.0 % (p = 0.041) and 5.3 ± 3.9 % (p = 0.005) reduction, respectively, in the inclined vs. non-inclined position. The inclined head position had lower hippocampi Dmin (10.45 ± 0.36 Gy), Dmax (13.70 ± 0.25 Gy), and Dmean (12.01 ± 0.38 Gy) values vs. the non-inclined head position (Dmin = 12.07 ± 1.07 Gy; Dmax = 15.70 ± 1.25 Gy; Dmean = 13.91 ± 1.01 Gy), with 12.8 ± 8.9 % (p = 0.007), 12.2 ± 6.8 % (p = 0.003), and 13.2 ± 7.2 % (p = 0.002) reductions, respectively. Mean Dmax for the lenses was 6.34 ± 0.72 Gy and 7.60 ± 0.46 Gy, respectively, with a 16.3 ± 10.8 % reduction in the inclined position (p = 0.004). Dmax for the optic nerve and Dmean for the eyeballs also decreased by 7.0 ± 5.9 % (p = 0.015) and 8.4 ± 7.2 % (p = 0.015), respectively. CONCLUSION: Inclining the head position to approximately 11° during HS-WBRT using VMAT improved dose distribution in the planning target volume and allowed lower doses to the hippocampi and optic apparatus.

Comparison of Dosimetric Performance among Commercial Quality Assurance Systems for Verifying Pretreatment Plans of Stereotactic Body Radiotherapy Using Flattening-Filter-Free Beams.

The purpose of this study was to compare the performance of different commercial quality assurance (QA) systems for the pretreatment verification plan of stereotactic body radiotherapy (SBRT) with volumetric arc therapy (VMAT) technique using a flattening-filter-free beam. The verification for 20 pretreatment cancer patients (seven lung, six spine, and seven prostate cancers) were tested using three QA systems (EBT3 film, I'mRT MatriXX array, and MapCHECK). All the SBRT-VMAT plans were optimized in the Eclipse (version 11.0.34) treatment planning system (TPS) using the Acuros XB dose calculation algorithm and were delivered to the Varian TrueBeam® accelerator equipped with a high-definition multileaf collimator. Gamma agreement evaluation was analyzed with the criteria of 2% dose difference and 2 mm distance to agreement (2%/2 mm) or 3%/3 mm. The highest passing rate (99.1% for 3%/3 mm) was observed on the MapCHECK system while the lowest passing rate was obtained on the film. The pretreatment verification results depend on the QA systems, treatment sites, and delivery beam energies. However, the delivery QA results for all QA systems based on the TPS calculation showed a good agreement of more than 90% for both the criteria. It is concluded that the three 2D QA systems have sufficient potential for pretreatment verification of the SBRT-VMAT plan.

Outcomes and recurrence patterns according to breast cancer subtypes in Korean women.

The aim of this study was to evaluate the outcomes and patterns of recurrence in the different subtypes of breast cancer. We analyzed 1432 stage I-III breast cancer patients who had undergone surgery at Seoul National University Bundang Hospital between June 2003 and August 2011. Five subtypes were defined according to estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67. Overall survival (OS) and breast cancer-free interval (BCFI) rates were estimated using the Kaplan-Meier method. Site-specific recurrence was estimated using Gray's test. The median follow-up period was 53 months. There were 22 local recurrences, 18 cases of contralateral breast cancer, 19 regional nodal recurrences, and 70 distant metastases. The 5-year BCFIs by subtype were luminal B-HER2 (+), 94.2 %; luminal A, 93.9 %; luminal B-HER2 (-), 91.4 %; HER2, 83.1 %; and triple-negative, 81.9 % (p < 0.001). Cases with the luminal A had a 5-year OS rate of 98.3 % that was the longest compared to those of cases with luminal B-HER2 (-), 95.8 %; luminal B-HER2 (+), 98.0 %; HER2, 90.8 %; and triple-negative, 89.9 % (p < 0.001). The triple-negative had a higher rate of local recurrence at the first site than others (p = 0.013). HER2 and triple-negative had higher rates of nodal recurrence at the first site than others (p < 0.001). The outcomes and patterns of site-specific recurrence in Korean breast cancer patients were different for each subtype. Defining recurrence patterns by breast cancer subtypes can help determine the appropriate method of surveillance and treatment.

Elective pelvic versus prostate bed-only salvage radiotherapy following radical prostatectomy: A propensity score-matched analysis.

PURPOSE: To compare the impact of elective whole pelvic radiotherapy (WPRT) versus prostate bed-only radiotherapy (PBRT) on biochemical relapse-free survival (bRFS) in prostate cancer patients treated with salvage radiotherapy following radical prostatectomy (RP). PATIENTS AND METHODS: In our database, 163 lymph node-negative prostate cancer patients who had undergone salvage radiotherapy (SRT) for biochemical relapse after RP between September 2004 and April 2012 were identified. PBRT was administered to 134 patients (the PBRT group), while the remaining 29 patients (the WPRT group) received WPRT. RESULTS: Median follow-up was 57 months (range 18-122 months). In the propensity score-matched cohort, the 4-year bRFS of the WPRT group was significantly higher compared to the PBRT group (63.1 vs. 43.4%, p = 0.034). Subgroup analysis showed that the bRFS of patients who had two or more risk factors (seminal vesicle invasion, Roach score for lymph node invasion ≥ 45%, and number of harvested lymph nodes ≤ 5) and were treated with WPRT was significantly improved compared to those who received PBRT (hazard ratio, HR 0.33; 95% confidence interval, CI 0.13-0.83; p = 0.018). CONCLUSION: Elective WPRT for SRT may improve bRFS in patients with unfavorable risk factors. These results need to be confirmed by a prospective randomized trial.

Comparison of VMAT-SABR treatment plans with flattening filter (FF) and flattening filter-free (FFF) beam for localized prostate cancer.

The purpose of this study is to investigate the feasibility of using a flattening filter-free (FFF) beam with an endorectal balloon for stereotactic ablative body radiotherapy (SABR) of clinically localized prostate cancer. We assessed plans of SABR with volumetric-modulated arc therapy (VMAT) that used a flattening filter (FF) beam and an FFF beam and compared the verification results of dosimetric quality assurance for all pretreatment plans. A total of 20 patients with prostate cancer were enrolled in the study. SABR plans using VMAT with two full arcs were optimized in the Eclipse treatment planning system. All plans prescribed 42.7 Gy in 7 fractions of 6.1 Gy each. Four SABR plans were computed for each patient: two with FF beams and two with FFF beams of 6 and 10 MV. For all plans, the cumulative dose-volume histograms (DVHs) for the target volumes and organs at risk (OARs) were recorded and compared. Pretreatment quality assurance (QA) was performed using the I'mRT MatriXX system and radiochromic EBT3 film to verify treatment delivery, and gamma analysis was used to quantify the agreement between calculations and measurements. In addition, total monitor units (MUs) and delivery time were investigated as technical parameters of delivery. All four plans achieved adequate dose conformity to the target volumes and had comparable dosimetric data. The DVHs of all four plans for each patient were very similar. All plans were highly conformal with CI < 1.05 and CN > 0.90, and the doses were homogeneous (HI = 0.08-0.15). Sparing for the bladder and rectum was slightly better with the 10 MV FF and FFF plans than with the 6 MV FF and FFF plans, but the difference was negligible. However, there was no significant difference in sparing for the other OARs. The mean agreement with the 3%/3 mm criterion was higher than 97% for verifying all plans. For the 2%/2 mm criterion, the corresponding agreement values were more than 90%, which showed that the plans were acceptable. The mean MUs and delivery time used were 1701 ± 101 and 3.02 ± 0.17 min for 6 MV FF, 1870 ± 116 and 2.01 ± 0.01 min for 6 MV FFF, 1471 ± 86 and 2.68 ± 0.14 min for 10 MV FF, and 1619 ± 101 and 2.00 ± 0.00 min for 10MV FFF, respectively. In the current study, the dose distributions of the prostate SABR plans using 6 and 10 MV FFF beams were similar to those using 6 and 10 MV FF beams. However, this study confirmed that SABR treatment using an FFF beam had an advantage with respect to delivery time. In addition, all pretreatment plans were verified as acceptable and their results were comparable. Therefore, the results of this study suggest that the use of an FFF beam for prostate SABR is a feasible and efficient technique, if carefully applied.

P21 and CD166 as predictive markers of poor response and outcome after fluorouracil-based chemoradiotherapy for the patients with rectal cancer.

BACKGROUND: Pre-operative chemoradiotherapy (CRT) is the standard treatment in clinical stage T3/4 or node positive rectal cancer. However, there are no established biomarkers that can predict the pathological response and clinical outcome to CRT. METHODS: Immunohistochemical staining was performed in tissue arrays constructed from core tissue specimens taken before treatment and from operative specimens from 112 patients who received 5-FU based pre-operative CRT and surgery. Expression of Ki67, TS, BAX, EpCAM, p53, p21, EGFR, CD44, CD133, CD166, HIF1α and ALDH1 were assessed and correlated with tumor regression grades and disease free survival. RESULTS: Of the 112 patients (M/F 74/38, median age: 62), 20 (17.9%) patients achieved pathologic complete remission (pCR). In analyzing the associations between marker expressions and tumor regression grades, high p21 expression at the pretreatment biopsy was significantly associated with non-pCR (p = 0.022) and poor disease free survival (median DFS - low vs high p21: 75.8 vs 58.1 months, p = 0.002). In the multivariate analysis, high p21 expression level at the pre-treatment biopsy was significantly associated with poor DFS (p = 0.001, HR 6.14; 95% CI 2.03, 18.55). High CD166 expression level at the pretreatment biopsy was also associated with poor DFS (p = 0.003; HR 5.61; 95% CI 1.81, 17.35). CONCLUSION: These show high p21 and CD166 expression at the pretreatment biopsy were associated with tumor regression and poor prognosis in patients treated with 5-FU based CRT. Larger, prospective and functional studies are warranted to determine the role of p21 and CD166 as predictive biomarker of response to CRT.

Assessment of Bone Marrow Involvement in Extranodal NK/T-Cell Lymphoma: Positron Emission Tomography versus Bone Marrow Biopsy, and the Significance of Minimal Involvement by EBV+ Cells (KROG 18-09).

PURPOSE: This study aims to investigate the diagnostic significance of positron emission tomography/computed tomography (PET/CT) in assessing bone marrow (BM) involvement through a comparison of PET/CT findings with BM biopsy in extranodal natural killer/T-cell lymphoma. MATERIALS AND METHODS: The medical records of 193 patients were retrospectively reviewed. Patients were categorized as having early-stage (PET-ES) or advanced-stage (PET-AS) disease based on PET/CT results. The BM involvement was classified into three groups according to BM biopsy: gross BM involvement, minimal BM involvement (defined as the presence of a limited number of Epstein-Barr virus-positive cells in BM), and no involvement. Calculations of the accuracy of PET/CT in detecting BM involvement and analysis of the clinical outcomes (progression-free survival [PFS] and overall survival [OS]) according to the BM biopsy status were performed. RESULTS: PET/CT exhibited a sensitivity of 64.7% and a specificity of 96.0% in detecting gross BM involvement. For detecting any (both gross and minimal) BM involvement, the sensitivity was 30.4%, while the specificity was 99.0%. Only one patient (0.7%) demonstrated gross BM involvement among the PET-ES group. Survival outcomes of the PET-ES group with minimal BM involvement (3-year PFS, 55.6%; OS, 77.0%) were closer to those of the PET-ES group with no BM involvement (3-year PFS, 62.2%; OS, 80.6%) than to those of the PET-AS group (3-year PFS, 20.1%; OS, 29.9%). CONCLUSION: PET/CT exhibits high specificity, but moderate and low sensitivity in detecting gross and minimal BM involvement, respectively. The clinical significance of minimal BM involvement for patients in the PET-ES group may be limited.

Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial).

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

Pattern of practice for postoperative management of endometrial cancer in Korea: a survey by the Korean Gynecologic Oncology Group and the Korean Radiation Oncology Group (KGOG 2028-KROG 2104).

OBJECTIVE: This study aimed to investigate the current status of postoperative management of uterine endometrial cancer (EC) in Korea. METHODS: A mail survey was administered to members of the Korean Gynecologic Oncology Group and Korean Radiation Oncology Group. A total of 38 gynecologic cancer surgeons (GYNs) and 31 radiation oncologists (RO) in 43 institutions was responded. The questionnaire consisted of general questions for clinical decision and clinical case questions. The GYN and RO responses were compared using chi-square statistics. RESULTS: The 2 expert groups had similar responses for clinical decision based on the results of the Gynecologic Oncology Group (GOG)-249 and Postoperative Radiation Therapy for Endometrial Carcinoma-III trials in the early-stage EC. In contrast, the responses based on GOG-258 results differed, as GYNs most frequently opted for sequential chemotherapy (CTx) and radiotherapy (RT), while ROs preferred concurrent chemoradiotherapy in locally advanced stage (p<0.05). Based on the GOG-258, GYNs preferred CTx alone for adjuvant treatment of serous or clear cell adenocarcinoma histology, whereas ROs advocated for combined CTx and RT (sequential or concurrent). Among the clinical case questions, GYNs were more likely than ROs to choose CTx alone rather than the combination of CTx and RT (sequential or concurrent) as the answers to case questions representing patients with locally advanced stage or unfavorable histology (all p<0.05). CONCLUSION: The present study showed several different opinions of GYNs and ROs regarding adjuvant treatment for EC, particularly for adjuvant RT in advanced stage or unfavorable histology.

Adjuvant radiotherapy in node-negative salivary malignancies of the parotid gland: A multi-institutional analysis.

BACKGROUND AND PURPOSE: To determine the role of adjuvant radiotherapy (ART) in parotid gland cancer without nodal metastasis, we evaluated the survival outcomes, prognostic factors, and dose-response relationships in patients with node-negative parotid gland cancer patients. MATERIALS AND METHODS: Patients who underwent curative parotidectomy and were pathologically diagnosed with parotid gland cancer without regional or distant metastases between 2004 and 2019 were reviewed. The benefit of ART in terms of locoregional control (LRC) and progression-free survival (PFS) were evaluated. RESULTS: In total, 261 patients were included in the analysis. Of them, 45.2 % received ART. The median follow-up period was 66.8 months. Multivariate analysis revealed that histological grade and ART were independent prognostic factors for LRC and PFS (all p <.05). For patients with high-grade histology, ART was associated with a significant improvement in 5-year LRC (p =.005) and PFS (p =.009). Among patients with high-grade histology who completed RT, higher biologic effective dose (≥77 Gy10) significantly increased PFS (adjusted hazard ratio [HR], 0.10 per 1-Gy increase; 95 % confidence interval [CI], 0.02-0.58; p =.010). ART significantly improved LRC (p =.039) in patients with low-to-intermediate histological grade as well per multivariate analysis, and subgroup analyses revealed patients with T3-4 stage and close/positive resection margins (<1 mm) would benefit from ART. CONCLUSION: ART should be strongly recommended for patients with node-negative parotid gland cancer with high-grade histology in terms of disease control and survival. In patients with low-to-intermediate-grade disease, those with high T stage and incomplete resection margin benefit with ART.