Correction: Sung et al. Linear Tumor Regression of Rectal Cancer in Daily MRI during Preoperative Chemoradiotherapy: An Insight of Tumor Regression Velocity for Personalized Cancer Therapy. Cancers 2022, 14, 3749.

In the original publication [...].

Intensity-Modulated Radiation Therapy for Uterine Cervical Cancer to Reduce Toxicity and Enhance Efficacy - an Option or a Must?: A Narrative Review.

Radiotherapy (RT) is a fundamental modality in treatment of cervical cancer. With advancement of technology, conventional RT used for external beam radiotherapy (EBRT) for over half a century has been rapidly replaced with intensity-modulated radiation therapy (IMRT) especially during the last decade. This newer technique is able to differentiate the intensity of radiation within the same field, thus reduces the inevitable exposure of radiation to normal organs and enables better dose delivery to tumors. Recently, the American Society for Radiation Oncology has released a guideline for RT in cervical cancer. Although a section of the guideline recommends IMRT for the purpose of toxicity reduction, a thorough review of the literature is necessary to understand the current status of IMRT in cervical cancer. This narrative review updates the recent high-level evidences regarding the efficacy and toxicity of IMRT and provides a better understanding of the most innovative techniques currently available for EBRT enabled by IMRT.

Assessment of deep learning-based auto-contouring on interobserver consistency in target volume and organs-at-risk delineation for breast cancer: Implications for RTQA program in a multi-institutional study.

PURPOSE: To quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV. METHODS AND MATERIALS: In phase 1, two breast cancer cases were randomly selected and distributed to multiple institutions for contouring six clinical target volumes (CTVs) and eight OAR. In Phase 2, auto-contour sets were generated using a previously published DL Breast segmentation model and were made available for all participants. The difference in IOV of submitted contours in phases 1 and 2 was investigated quantitatively using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). The qualitative analysis involved using contour heat maps to visualize the extent and location of these variations and the required modification. RESULTS: Over 800 pairwise comparisons were analysed for each structure in each case. Quantitative phase 2 metrics showed significant improvement in the mean DSC (from 0.69 to 0.77) and HD (from 34.9 to 17.9 mm). Quantitative analysis showed increased interobserver agreement in phase 2, specifically for CTV structures (5-19 %), leading to fewer manual adjustments. Underlying IOV differences causes were reported using a questionnaire and hierarchical clustering analysis based on the volume of CTVs. CONCLUSION: DL-based auto-contours improved the contour agreement for OARs and CTVs significantly, both qualitatively and quantitatively, suggesting its potential role in minimizing radiation therapy protocol deviation.

Impact of radiation on immune cells in patients with low-grade brain tumor: Identifying critical factors affecting lymphopenia and neutrophil-to-lymphocyte ratio.

PURPOSE: Studies about the effect of radiation therapy (RT) on immune cells are usually limited to a high-grade glioma mostly exposed to chemotherapy and a high dose of steroid which also could affect immune cells. The purpose of this retrospective analysis of low-grade brain tumor patients treated by RT alone is to determine significant factors influencing neutrophil-to-lymphocyte ratio (NLR), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC). MATERIALS AND METHODS: A total of 41 patients who received RT between 2007 and 2020 were analyzed. Patients who received chemotherapy and high-dose of steroid were excluded. ANC and ALC were collected before starting RT (baseline) and within one-week before ending RT (post-treatment). Changes of ANC, ALC, and NLR between baseline and post-treatment were calculated. RESULTS: ALC decreased in 32 patients (78.1%). NLR increased in 31 patients (75.6%). No patients developed grade 2 or higher hematologic toxicities. The decrease of ALC was significantly correlated with the dose to brain V15 in a simple and multiple linear regression (p = 0.043). Brain V10 and V20 adjacent to V15 were also marginally significant factors determining the reduction of lymphocytes (p = 0.050 and p = 0.059, respectively). However, it was difficult to find predictive factors affecting changes of ANC and NLR. CONCLUSION: In low-grade brain tumor patients who are treated by RT alone, ALC decreased and NLR increased in three-fourth of patients, although the magnitude was minimal. The decrease of ALC was mainly affected by low dose to the brain. However, RT dose was not correlated with changes of ANC or NLR.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Recommendation Using the Delphi Method (Version 2023.1).

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the need for appropriate treatment guidelines for patients with brain tumors was indispensable due to the lack and limitations of medical resources. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. METHODS: The KSNO Guideline Working Group was composed of 22 multidisciplinary experts on neuro-oncology in Korea. In order to reach consensus among the experts, the Delphi method was used to build up the final recommendations. RESULTS: All participating experts completed the series of surveys, and the results of final survey were used to draft the current consensus recommendations. Priority levels of surgery and radiotherapy during crises were proposed using appropriate time window-based criteria for management outcome. The highest priority for surgery is assigned to patients who are life-threatening or have a risk of significant impact on a patient's prognosis unless immediate intervention is given within 24-48 hours. As for the radiotherapy, patients who are at risk of compromising their overall survival or neurological status within 4-6 weeks are assigned to the highest priority. Curative-intent chemotherapy has the highest priority, followed by neoadjuvant/adjuvant and palliative chemotherapy during a crisis period. Telemedicine should be actively considered as a management tool for brain tumor patients during the mass infection crises such as the COVID-19 pandemic. CONCLUSION: It is crucial that adequate medical care for patients with brain tumors is maintained and provided, even during times of crisis. This guideline will serve as a valuable resource, assisting in the delivery of treatment to brain tumor patients in the event of any future crisis.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Survey About Specific Clinical Scenarios (Version 2023.1).

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period. METHODS: The KSNO Guideline Working Group consisted of 22 multidisciplinary experts on neuro-oncology in Korea. In order to confirm a consensus reached by the experts, opinions on 5 specific clinical scenarios about the management of brain tumor patients during the crisis period were devised and asked. To build-up the consensus process, Delphi method was employed. RESULTS: The summary of the final consensus from each scenario are as follows. For patients with newly diagnosed astrocytoma with isocitrate dehydrogenase (IDH)-mutant and oligodendroglioma with IDH-mutant/1p19q codeleted, observation was preferred for patients with low-risk, World Health Organization (WHO) grade 2, and Karnofsky Performance Scale (KPS) ≥60, while adjuvant radiotherapy alone was preferred for patients with high-risk, WHO grade 2, and KPS ≥60. For newly diagnosed patients with glioblastoma, the most preferred adjuvant treatment strategy after surgery was radiotherapy plus temozolomide except for patients aged ≥70 years with KPS of 60 and unmethylated MGMT promoters. In patients with symptomatic brain metastasis, the preferred treatment differed according to the number of brain metastasis and performance status. For patients with newly diagnosed atypical meningioma, adjuvant radiation was deferred in patients with older age, poor performance status, complete resection, or low mitotic count. CONCLUSION: It is imperative that proper medical care for brain tumor patients be sustained and provided, even during the crisis period. The findings of this consensus survey will be a useful reference in determining appropriate treatment options for brain tumor patients in the specific clinical scenarios covered by the survey during the future crisis.

Comparison of initial and sequential salvage brain-directed treatment in patients with 1-4 vs. 5-10 brain metastases from breast cancer (KROG 16-12).

PURPOSE: We aimed to compare the initial and salvage brain-directed treatment and overall survival (OS) between patients with 1-4 brain metastases (BMs) and those with 5-10 from breast cancer (BC). We also organized a decision tree to select the initial whole-brain radiotherapy (WBRT) for these patients. METHODS: Between 2008 and 2014, 471 patients were diagnosed with 1-10 BMs. They were divided into two groups based on the number of BM: 1-4 BMs (n = 337) and 5-10 BMs (n = 134). Median follow-up duration was 14.0 months. RESULTS: Stereotactic radiosurgery (SRS)/fractionated stereotactic radiotherapy (FSRT) was the most common treatment modality (n = 120, 36%) in the 1-4 BMs group. In contrast, 80% (n = 107) of patients with 5-10 BMs were treated with WBRT. The median OS of the entire cohort, 1-4 BMs, and 5-10 BMs was 18.0, 20.9, and 13.9 months, respectively. In the multivariate analysis, the number of BM and WBRT were not associated with OS, whereas triple-negative BC and extracranial metastasis decreased OS. Physicians determined the initial WBRT based on four variables in the following order: number and location of BM, primary tumor control, and performance status. Salvage brain-directed treatment (n = 184), mainly SRS/FSRT (n = 109, 59%), prolonged OS by a median of 14.3 months. CONCLUSION: The initial brain-directed treatment differed notably according to the number of BM, which was chosen based on four clinical factors. In patients with ≤ 10 BMs, the number of BM and WBRT did not affect OS. The major salvage brain-directed treatment modality was SRS/FSRT and increased OS.

Prognostic impact of 18F-FDG PET/CT in pathologic stage II invasive ductal carcinoma of the breast: re-illuminating the value of PET/CT in intermediate-risk breast cancer.

BACKGROUND: The aim of this study is to investigate the impact of 18F-FDG PET/CT on prognosis of stage II invasive ductal carcinoma (IDC) of the breast primarily treated with surgery. METHODS: The clinical records of 297 consecutive IDC with preoperative PET/CT and pathologically staged II in surgery from 2013 to 2017 were retrospectively reviewed. The maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), tumor-to-liver ratio (TLR), and metabolic tumor volume (MTV) were measured. Association of clinicopathologic factors (age, T stage, N stage, AJCC pathologic stage of IIA or IIB, pathologic prognostic stage, grade, hormonal receptor status, HER2 status, Ki-67, and adjuvant therapy) and PET parameters with DFS was assessed using the Cox proportional hazards model. RESULTS: There were 35 recurrences and 10 deaths at a median follow-up of 49 months (range 0.8 ~ 87.3). All PET parameters were significantly associated with DFS in univariate analysis but in multivariate analysis, SUVpeak was the only factor significantly associated with DFS (hazard ratio 2.58, 95% confidence interval 1.29-5.15, P = 0.007). In cohorts with higher values of SUVpeak or TLR, patients who received adjuvant chemotherapy had significantly superior DFS. CONCLUSION: Metabolic parameters derived from preoperative PET/CT was significantly associated with recurrence in stage II IDC primarily treated with surgery. PET/CT can be a powerful prognostic tool in conjunction with novel staging systems and current biomarkers for patients undergoing contemporary therapy. Our results urge to reconsider the currently underestimated value of PET/CT confined to diagnostic aspect and to newly recognize its prognostic impact in these intermediate-risk breast cancer.

Quality Assessment and Trend for Breast Cancer Treatment Practice across South Korea Based on Nationwide Analysis of Korean Health Insurance Data during 2013-2017.

PURPOSE: Quality assessment of breast cancer treatment in South Korea showed the upward standardization of the grade since 2013, but treatment disparities still have existed. This study analyzed the five year trend between 2013 and 2017 in the assessment of breast cancer treatment practice using the Korean health insurance data. Materials and Methods: All the medical records including surgery, chemotherapy, and radiotherapy for 7,354 patients a year on average were evaluated. Twenty indices were consisted of one structural, 17 process-related, and 2 result-related factors. We calculated the coefficient of variation (CV) annually to determine the variation in adherence rate of evaluation indices according to the type of institution (advanced vs. general hospital vs. clinic). RESULTS: Based on the initial assessment in 2013, 10 out of 20 indicators showed significant variation among the types of institutions with a CV of less than 0.1%. Six of them had a CV decline of less than 0.1%. The CV was still 0.1% or higher in the four indicators, including the composition of professional staff, the implementation of target therapy, the average length of hospital stay, and the hospitalization cost. Regarding the first-grade of assessment, there was a statistically significant relationship between the institution type (p=0.029) and region (metropolitan vs. province, p<0.001). CONCLUSION: There were disparities in the structural and systemic treatment factors depending on the institutional type. The quality improvement of the regional institutions and multidisciplinary experts for breast cancer is necessary.

Effect of total intravenous versus inhalation anesthesia on long-term oncological outcomes in patients undergoing curative resection for early-stage non-small cell lung cancer: a retrospective cohort study.

BACKGROUND: Propofol-based total intravenous anesthesia (TIVA) improves long-term outcomes after cancer surgery compared with inhalation anesthesia. However, its effect on patients undergoing non-small cell lung cancer (NSCLC) surgery remains unclear. We aimed to compare the oncological outcomes of TIVA and inhalation anesthesia after curative resection of early-stage NSCLC. METHODS: We analyzed the medical records of patients diagnosed with stage I or II NSCLC who underwent curative resection at a tertiary university hospital between January 2010 and December 2017. The primary outcomes were recurrence-free survival (RFS) and overall survival (OS) according to anesthesia type. RESULTS: We included 1,508 patients with stage I/II NSCLC. The patients were divided into the TIVA (n = 980) and Inhalation (n = 528) groups. The two groups were well-balanced in terms of baseline clinical characteristics. The TIVA group demonstrated significantly improved RFS (7.7 years, 95% CI [7.37, 8.02]) compared with the Inhalation group (6.8 years, 95% CI [6.30, 7.22], P = 0.003). Similarly, TIVA was superior to inhalation agents with respect to OS (median OS; 8.4 years, 95% CI [8.08, 8.69] vs. 7.3 years, 95% CI [6.81, 7.71]; P < 0.001). Multivariable Cox regression analysis revealed that TIVA was an independent prognostic factor related to recurrence (hazard ratio [HR]: 1.24, 95% CI [1.04, 1.47], P = 0.014) and OS (HR: 1.39, 95% CI [1.12, 1.72], P = 0.002). CONCLUSIONS: Propofol-based TIVA was associated with better RFS and OS than inhalation anesthesia in patients with stage I/II NSCLC who underwent curative resection.

Current Evidence of a Deintensification Strategy for Patients with HPV-Related Oropharyngeal Cancer.

Human papillomavirus (HPV)-related oropharyngeal cancer differs from HPV-negative oropharyngeal cancer in terms of etiology, epidemiology, and prognosis. Younger and lower comorbidity patient demographics and favorable prognosis allow HPV-related oropharyngeal cancer patients to anticipate longer life expectancy. Reducing long-term toxicities has become an increasingly important issue. Treatment deintensification to reduce toxicities has been investigated in terms of many aspects, and the reduction of radiotherapy (RT) dose in definitive treatment, replacement of platinum-based chemotherapy with cetuximab, response-tailored dose prescription after induction chemotherapy, and reduction of adjuvant RT dose after transoral surgery have been evaluated. We performed a literature review of prospective trials of deintensification for HPV-related oropharyngeal cancer. In phase II trials, reduction of RT dose in definitive treatment showed comparable survival outcomes to historical results. Two phase III randomized trials reported inferior survival outcomes for cetuximab-based chemoradiation compared with cisplatin-based chemoradiation. In a randomized phase III trial investigating adjuvant RT, deintensified RT showed noninferior survival outcomes in patients without extranodal extension but worse survival in patients with extranodal extension. Optimal RT dosage and patient selection require confirmation in future studies. Although many phase II trials have reported promising outcomes, the results of phase III trials are needed to change the standard treatment. Since high-level evidence has not been established, current deintensification should only be performed as part of a clinical study with caution. Implementation in clinical practice should not be undertaken until evidence from phase III randomized trials is available.

Linear Tumor Regression of Rectal Cancer in Daily MRI during Preoperative Chemoradiotherapy: An Insight of Tumor Regression Velocity for Personalized Cancer Therapy.

Objective: Neoadjuvant chemoradiotherapy (CCRT) is current standards of care for locally advanced rectal cancer. The precise and thorough investigation of a tumor during the full course of CCRT by means of daily MRI can provide an idea on real-time treatment sensitivity in addition to tumor biology. Tumor volumetry from daily MRI during CCRT may allow patient-driven treatment decisions. Material and Methods: Patients diagnosed with cT3-4 and/or cN+ rectal adenocarcinoma undergoing preoperative CCRT with capecitabine on the pelvis up to 50 Gy in 25 daily fractions from November 2018 to June 2019 were consecutively included. Rectal tumor volume was uniformly measured by a single physician (YKK) in daily 0.35T MRI obtained with MR-guided linear accelerator. Primary endpoint was to assess the pattern of tumor volume regression throughout the full course of CCRT using daily registration MRI. Secondary endpoint was to assess the effect of tumor regression velocity on disease-free survival (DFS). Tumor regression velocity (cc) per fraction of each patient was calculated using the simple regression analysis of tumor volumes from fraction 1 to fraction 25. Results: Twenty patients were included. Daily tumor volumetry demonstrated linear tumor regression during CCRT. The tumor regression velocity of all 20 patients was 2.40 cc per fraction (R2 = 0.93; p < 0.001). The median tumor regression velocity was 1.52 cc per fraction. Patients with tumor regression velocity ≥ 1.52 cc per fraction were grouped as rapid regressors (N = 9), and those with tumor regression velocity < 1.52 cc per fraction were grouped as slow regressors (N = 11). Rapid regressors had greater tumor regression velocity (4.58 cc per fraction) compared to that of slow regressors (0.78 cc per fraction) with statistical significance (p < 0.001). The mean DFS of rapid regressors was 36.8 months, numerically longer than the 31.9 months of slow regressors (p = 0.400) without statistical significance. Rapid regressors had numerically superior DFS rate compared to slow regressors without statistical significance. The 2-year DFS was 88.9% for rapid regressors and 72.7% for slow regressors, respectively (p = 0.400). Conclusion: This study is the first observation of linear tumor regression in daily MRI during the preoperative CCRT of locally advanced rectal cancer. Daily tumor regression velocity discriminated DFS, although without statistical significance. This study with a phenomenal approach is hypothesis-generating. Nevertheless, the potential of CCRT from therapeutics to a newer level, the "theranostics", has been inceptively suggested. Further validation studies for the value of daily tumor volumetry on treatment decisions are warranted.

Current trend of radiotherapy for glioblastoma in the elderly: a survey study by the brain tumor Committee of the Korean Radiation Oncology Group (KROG 21-05).

BACKGROUND: To investigate the current variability in radiotherapy practice for elderly glioblastoma patients. METHODS: A questionnaire comprising general information on elderly glioblastoma, treatment selection, radiotherapy and 16 clinical case-scenario-based questions (based on age, performance, extent of resection and MGMT promoter methylation) was sent to brain tumor radiation oncologists. RESULTS: Twenty-one responses were recorded. Most (71.4%) stated that 70 years is an adequate cut-off for 'elderly' individuals. The most preferred hypofractionated short-course radiotherapy schedule was 40-45 Gy over 3 weeks (81.3%). The median margin for high-dose target volume was 5 mm (range, 0-20 mm) from the T1-enhancement for short-course radiotherapy. The case-scenario-based questions revealed a near-perfect consensus on 6-week standard radiotherapy plus concurrent/adjuvant temozolomide as the most appropriate adjuvant treatment in good performing patients aged 65-70 years, regardless of surgery and MGMT promoter methylation. Notably, in 75-year-old patients with good performance, the most preferred treatment was 6-week radiotherapy (81.0-90.5%) plus concurrent/adjuvant temozolomide (71.4-95.2%) rather than short-course radiotherapy or radiotherapy alone. Although the use of 3-week short-course radiotherapy increased with age and decreased performance status (all P < 0.05), 6-week radiotherapy was adopted in a significant proportion of responders (14.3-23.8%) even for wheelchair-bound, 75-year-old patients. Temozolomide use was affected by age, performance and MGMT promoter (all P < 0.05). CONCLUSIONS: A high level of consensus was observed in treating elderly glioblastoma patients with good performance status. However, the variability increased, especially for older patients and those with poor performance. This study serves as a basis for designing future clinical trials in elderly glioblastoma.

Prognostic Impact of Total Lesion Glycolysis (TLG) from Preoperative 18F-FDG PET/CT in Stage II/III Colorectal Adenocarcinoma: Extending the Value of PET/CT for Resectable Disease.

We investigated the prognostic role of metabolic parameters from preoperative 18F-FDG PET/CT in stage II/III colorectal adenocarcinoma. A total of 327 stage II/III colorectal adenocarcinoma patients who underwent curative resection were included. The maximal standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were analyzed for optimal cut-offs and their effect on DFS. Differences in DFS rates and hazard ratios for DFS between cut-offs were statistically significant in SUVmax, MTV2.5, MTV3, TLG 2.5, TLG3, and TLG30%. Factors significantly related to DFS in univariate Cox regression were age, sex, stage, preoperative CEA, SUVmax, MTV2.5, MTV3, TLG2.5, TLG3, and TLG30%. Age, sex, preoperative CEA, and TLG2.5 (p = 0.009) sustained statistically significant difference in multivariate analysis. The 1-, 3-, and 5-year DFS rates for TLG2.5 ≤ 448.5 were 98.1%, 79.6%, and 74.8%, significantly higher than 78.4%, 68.5%, and 61.1% of TLG2.5 > 448.5, respectively (p = 0.012). TLG, a parameter indicating both the metabolic activity and metabolic volume, was the strongest predictor independently associated with DFS, among several PET parameters with statistical significance. These results suggest the potential prognostic value of preoperative 18F-FDG PET/CT in stage II/III resectable colorectal cancer.

The Pattern of Care for Brain Metastasis from Breast Cancer over the Past 10 Years in Korea: A Multicenter Retrospective Study (KROG 16-12).

PURPOSE: We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea. MATERIALS AND METHODS: We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients). RESULTS: Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance. CONCLUSION: The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.

Serum conversion pattern of SCC-Ag levels between pre- and post-chemoradiotherapy predicts recurrence and metastasis in cervical cancer: a multi-institutional analysis.

The value of squamous-cell carcinoma antigen (SCC-Ag) as a tumor marker for cervical cancer is controversial because it is not elevated (> 2 ng/mL) in a quarter of patients at diagnosis. Two hundred ninety one IB-IVA cervical squamous cell-carcinoma patients who underwent definitive chemoradiotherapy (CRT) were included in four tertiary institutions. Serum conversion pattern between pre- and post-treatment SCC-Ag levels was categorized into the following three arms: (1) Consistent Seronegative arm (both ≤ 2 ng/mL); (2) Negative Conversion arm (from > 2 ng/mL to ≤ 2 ng/mL); and (3) Consistent Seropositive arm (both > 2 ng/mL). Median follow-up time was 40.3 months. For Consistent Seronegative (N = 67), Negative Conversion (N = 165), and Consistent Seropositive (N = 59) arms, the 3-year recurrence-free survival (RFS) rates were 79.4%, 62.0%, and 48.4% (P < 0.001) and the 3-year overall survival (OS) rates were 86.3%, 80.6%, and 58.7% (P = 0.001), respectively. The serum conversion pattern of SCC-Ag between pre- and post-treatment was the most significant and potent prognostic factor of RFS (P = 0.001) and OS (P = 0.007) on the multivariate analysis. Simply checking whether SCC-Ag level is above or below 2 ng/mL before and after definitive CRT can provide clinicians with a simple rule-of-thumb for prediction of disease outcome in cervical cancer patients.

New brain metastases after whole-brain radiotherapy of initial brain metastases in breast cancer patients: the significance of molecular subtypes (KROG 16-12).

PURPOSE: To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). METHODS: In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149). RESULTS: In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2-, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p < 0.001) according to molecular subtype (HR+/HER2-, 42% reduction at 1 year, p < 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis revealed an increased risk of new BM for the following factors: shorter intervals between primary BC diagnoses and BM (p = 0.031); TNBC (relative to HR+/HER2-) (p = 0.016); presence of extracranial metastases (p = 0.019); number of BM (>4) (p < 0.001); and BM in both tentorial regions (p = 0.045). Anti-HER2 therapy in HER2+ patients (p = 0.013) and initial use of WBRT (p < 0.001) significantly lowered new BM development. CONCLUSIONS: Tumor molecular subtypes were associated with both rates of new BM development and the effectiveness of initial WBRT. Anti-HER2 therapy in HER2+ patients significantly lowered new BM occurrence.

Impact of radiation dose on complications among women with breast cancer who underwent breast reconstruction and post-mastectomy radiotherapy: A multi-institutional validation study.

PURPOSE: Emerging data suggest that higher radiation doses in post-mastectomy radiotherapy may be associated with an increased risk of reconstruction complications. This study aimed to validate previous findings regarding the impact of radiation dose on complications among women with breast cancer using a multi-center dataset. METHODS: Fifteen institutions participated, and women with breast cancer who received radiotherapy after either autologous or prosthetic breast reconstruction were included. The primary endpoint was major post-radiation therapy complications requiring re-operation for explantation, flap failure, or bleeding control. RESULTS: In total, 314 patients were included. Radiotherapy was performed using both conventional fractionation and hypofractionation in various schedules. The range of the radiation therapy dose in Equivalent Dose in 2 Gy fractions (EQD2; α/ß = 3.5) varied from 43.4 to 71.0 Gy (median dose: 48.6 Gy). Boost radiation therapy was administered to 49 patients. Major post-radiation therapy complications were observed in 24 (7.6%) patients. In multivariate analysis, an increasing EQD2 per Gy (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.26-1.98; p < 0.001), current smoking status (OR: 25.48, 95% CI: 1.56-415.65; p = 0.023), and prosthetic breast reconstruction (OR: 9.28, 95% CI: 1.84-46.70; p = 0.007) were independently associated with an increased risk of major complications. CONCLUSION: A dose-response relationship between radiation dose and the risk of complications was validated in this multi-center dataset. In this context, we hypothesize that the use of hypofractionated radiotherapy (40 Gy in 15 fractions) may improve breast reconstruction outcomes. Our multi-center prospective observational study (NCT03523078) is underway to further validate this hypothesis.