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

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

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.

Validation of a nomogram for predicting the risk of lymphedema following contemporary treatment for breast cancer: a large multi-institutional study (KROG 20-05).

PURPOSE: We previously constructed a nomogram for predicting the risk of arm lymphedema following contemporary breast cancer treatment. This nomogram should be validated in patients with different background characteristics before use. Therefore, we aimed to externally validate the nomogram in a large multi-institutional cohort. METHODS: Overall, 8835 patients who underwent breast cancer surgery during 2007-2017 were identified. Data of variables in the nomogram and arm lymphedema were collected. The nomogram was validated externally using C-index and integrated area under the curve (iAUC) with 1000 bootstrap samples and by calibration plots. RESULTS: Overall, 1377 patients (15.6%) developed lymphedema. The median time from surgery to lymphedema development was 11.4 months. Lymphedema rates at 2, 3, and 5 years were 11.2%, 13.1%, and 15.6%, respectively. Patients with lymphedema had significantly higher body mass index (median, 24.1 kg/m2 vs. 23.4 kg/m2) and a greater number of removed nodes (median, 17 vs. 6) and more frequently underwent taxane-based chemotherapy (85.7% vs. 41.9%), total mastectomy (73.1% vs. 52.1%), conventionally fractionated radiotherapy (71.9% vs. 54.2%), and regional nodal irradiation (70.7% vs 22.4%) than those who did not develop lymphedema (all P < 0.001). The C-index of the nomogram was 0.7887, and iAUC was 0.7628, indicating good predictive accuracy. Calibration plots confirmed that the predicted lymphedema risks were well correlated with the actual lymphedema rates. CONCLUSION: This nomogram, which was developed using factors related to multimodal breast cancer treatment and was validated in a large multi-institutional cohort, can well predict the risk of breast cancer-related lymphedema.

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

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

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

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

Hypofractionated volumetric-modulated arc therapy for breast cancer: A propensity-score-weighted comparison of radiation-related toxicity.

We assessed the clinical benefit of combining volumetric-modulated arc therapy (VMAT) and hypofractionated radiotherapy (HF-RT) considering the incidence of radiation-related toxicities. After a retrospective review for breast cancer patients treated with adjuvant RT between 2005 and 2017, a total of 4209 patients treated with three-dimensional conventional fractionation (CF-3D, 50.4 Gy/28 fractions) and 1540 patients treated with HF-RT (768 received HF-3D; 772, HF-VMAT; 40 Gy/15 fractions) were included. A total of 2229 patients (38.8%) received regional node irradiation (RNI): 1642 (39.0%), 167 (21.7%) and 420 (54.4%) received RNI via CF-3D, HF-3D and HF-VMAT, respectively. Acute/subacute and late toxicities were evaluated. Propensity scores were calculated via logistic regression. Grade 2+ acute/subacute toxicities was the highest in CF-3D group (15.0%, 2.6% and 1.6% in CF-3D, HF-3D and HF-VMAT, respectively; P < .001). HF-VMAT reduced Grade 2+ acute/subacute toxicities significantly compared to CF-3D (odds ratio [OR] 0.11, P < .001) and HF-3D (OR 0.45, P = .010). The 3-year cumulative rate of late toxicities was 18.0% (20.1%, 10.9% and 13.4% in CF-3D, HF-3D and HF-VMAT, respectively; P < .001). On sensitivity analysis, the benefit of HF-VMAT was high in the RNI group. Acute and late toxicities were fewer after HF-VMAT than after HF-3D or CF-3D, especially in women who underwent RNI.

Risk of Lymphedema Following Contemporary Treatment for Breast Cancer: An Analysis of 7617 Consecutive Patients From a Multidisciplinary Perspective.

OBJECTIVE: The aim of this study was to identify the comprehensive risk factors for lymphedema, thereby enabling a more informed multidisciplinary treatment decision-making. SUMMARY BACKGROUND DATA: Lymphedema is a serious long-term complication in breast cancer patients post-surgery; however, the influence of multimodal therapy on its occurrence remains unclear. METHODS: We retrospectively collected treatment-related data from 5549 breast cancer patients who underwent surgery between 2007 and 2015 at our institution. Individual radiotherapy plans were reviewed for regional nodal irradiation (RNI) field design and fractionation type. We identified lymphedema risk factors and used them to construct nomograms to predict individual risk of lymphedema. Nomograms were validated internally using 100 bootstrap samples and externally using 2 separate datasets of 1877 Asian and 191 Western patients. RESULTS: Six hundred thirty-nine patients developed lymphedema during a median follow-up of 60 months. The 3-year lymphedema incidence was 10.5%; this rate increased with larger irradiation volumes (no RNI vs RNI excluding axilla I-II vs RNI including axilla I-II: 5.7% vs 16.8% vs 24.1%) and when using conventional fractionation instead of hypofractionation (13.5% vs 6.8%). On multivariate analysis, higher body mass index, larger number of dissected nodes, taxane-based regimen, total mastectomy, larger irradiation field, and conventional fractionation were strongly associated with lymphedema (all P < 0.001). Nomograms constructed based on these variables showed good calibration and discrimination internally (concordance index: 0.774) and externally (0.832 for Asian and 0.820 for Western patients). CONCLUSIONS: Trimodality breast cancer treatment factors interact to promote lymphedema. Lymphedema risk can be decreased by deintensifying node dissection, chemotherapy regimen, and field and dose of radiotherapy. Deescalation strategies on a multidisciplinary basis might minimize lymphedema risk.

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.

The mortality rate of Parkinson's disease and related comorbidities: a nationwide population-based matched cohort study in Korea.

BACKGROUND: previous studies on mortality of Parkinson's disease (PD) enrolled a relatively small number of participants and were conducted in western countries. The objective of this study was to evaluate mortality rate of PD using a large nationwide cohort in Korea and to evaluate effects comorbidities have on mortality in PD. METHODS: the nationwide population-based cohort study was conducted using the Korean National Health Insurance Service-National Sample Cohort data. Patients with a primary diagnosis of PD were selected from the database. A matched cohort without PD was enrolled through randomly matching patients by sex, age, year of diagnosis, residential area and income level to the PD group with a ratio of 1:9. The Cox proportional hazard model was used to assess mortality risk between the two cohorts. A logistic regression analysis was used to identify mortality risk factors in PD cohort. RESULTS: in total, 25,620 patients were enrolled. The Cox proportional regression model had an adjusted hazard ratio of 2.479 [95% confidence interval (CI), 2.272-2.704] for mortality in PD cohort. Comorbidities, such as ischaemic stroke [odds ratios (OR) = 2.314, 95% CI, 1.895-2.824], haemorrhagic stroke (OR = 2.281, 95% CI, 1.466-3.550) and chronic obstructive pulmonary disease (OR = 1.307, 95% CI, 1.048-1.630) were associated with increased mortality, whereas dyslipidemia (OR = 0.285, 95% CI, 0.227-0.358) was negatively correlated with mortality. CONCLUSION: over the 10 year follow-up period, the PD cohort's mortality rate was 2.5 times higher than the comparison cohort. Understanding the effects that comorbidities have on morality in PD would be useful for predicting mortality in patients with PD.

Use of bevacizumab before or after radiotherapy increases the risk of fistula formation in patients with cervical cancer.

OBJECTIVE: Several reports have documented the risk of fistula formation after bevacizumab in patients previously treated with radiation therapy. The aim of this study was to investigate the risk of fistula formation with bevacizumab and radiotherapy compared with radiotherapy alone. METHODS: We retrospectively analyzed patients with stage I-IV cervical cancer between January 2013 and December 2018. Patients who had a history of pelvic radiotherapy, who were treated with intracavitary brachytherapy alone, received radiotherapy at another hospital, received concurrent bevacizumab and radiotherapy, or had missing follow-up data or a short follow-up period (<6 months) were excluded. The fistula rates were compared between the groups using the Cox proportional hazards model and propensity score analyses. RESULTS: A total of 302 patients were included in the study: 249 patients were treated with definitive or adjuvant radiotherapy, and 53 patients were treated with radiotherapy before or after bevacizumab. With a median follow-up of 35.9 (IQR 22.8-53.5) months, the 3 year cumulative fistula incidence rate was significantly higher in the radiotherapy + bevacizumab group than in the radiotherapy group (27.0% vs 3.0%, p<0.001). Bevacizumab administration was significantly associated with fistula formation in the multivariable adjusted model (HR 4.76, 95% CI 1.71 to 13.23) and three propensity score adjusted model (all p<0.05). Biologically equivalent dose in 2 Gy fractions for 2 cc of the rectum more than 76 Gy was also associated with fistula formation (HR 4.30, 95% CI 1.52 to 12.18). Additionally, a 10 month interval between radiotherapy and bevacizumab reduced the incidence of fistula formation in the radiotherapy + bevacizumab group (p=0.032). CONCLUSIONS: In patients with cervical cancer treated with pelvic radiotherapy, the addition of bevacizumab substantially increased the risk of fistula formation. Physicians should perform pelvic radiotherapy in combination with bevacizumab with caution; moreover, close monitoring for fistula formation is warranted in these patients.

Hip Fracture in Patients with Parkinson's Disease and Related Mortality: A Population-Based Study in Korea.

INTRODUCTION: Patients with Parkinson's disease (PD) are prone to falls, thereby increasing the risk of fractures and mortality. This population-based study investigated the risk of hip fractures and their effect on mortality in patients with PD in Korea. METHODS: National Health Insurance Service-National Sample Cohort data were used. Patients newly diagnosed with PD between 2006 and 2015 and age- and sex-matched individuals were classified into the PD group and the comparison group, respectively, with a 1:9 ratio. The Cox proportional hazards model was used to calculate hazard ratios (HRs), and the Kaplan-Meier method to identify survivorship. RESULTS: In total, 26,570 individuals were enrolled in the study: 2,657 in the PD cohort and 23,913 in the matched comparison cohort. The PD group had about a 2 times higher risk of hip fracture than the comparison group (3.95 vs. 1.94%, p < 0.001). According to sex, the difference between the PD and comparison groups for the risk of hip fracture was greater in males than in females. The highest difference in HR for hip fracture between the PD and comparison groups was found in individuals aged between 60 and 69 years. Regarding post-fracture mortality in patients with PD, the mortality risk was twice as high in the patients with hip fracture than in those without. The effect of hip fracture on mortality between these 2 groups was also the highest in individuals aged between 60 and 69 years. CONCLUSION: The PD group showed an approximately 2 times higher risk of hip fracture compared with the comparison group, and the post-fracture mortality rate was 2 times higher in the patients with PD with hip fracture than in those without. Those aged 60-69 years were associated with the highest risk of hip fracture and post-hip fracture mortality among patients with PD.

Tumor immune microenvironment in cancer patients with leukocytosis.

Tumor-related leukocytosis (TRL) is correlated with poor survival in various types of cancers, but the microenvironment of TRL-associated human tumors has not been fully elucidated. Here, we aimed to characterize the immune microenvironment of cancer patients with TRL. The transcriptional signatures of tumor tissues obtained from cervical cancer patients with (TRLpos) and without TRL (TRLneg) were compared. As a surrogate for TRL diagnosis, a leukocytosis signature (LS) score was derived using genes differentially expressed between TRLpos and TRLneg tumors. The immunological profiles of patients in the TCGA database with high (LShigh) or low LS scores were compared. TRLpos tumors were transcriptionally distinct from TRLneg tumors, exhibiting up-regulation of radioresistance and down-regulation of adaptive immune response-related genes. In the TCGA cervical cancer cohort (n = 303), patients with high LS had inferior survival rates compared to those with low LS (P = 0.023). LShigh tumors were enriched in radioresistance, wound healing, and myeloid-derived suppressor cell (MDSC) signatures and had a higher infiltration of M2 macrophages and a lower infiltration of M1 macrophages and lymphocytes. LShigh tumors also expressed higher levels of CXCR2 chemokines, CSF2, and CSF3. In the pan-cancer cohort (n = 9984), LShigh tumors also exhibited poor survival, signatures of a suppressive immune microenvironment, and higher expression of CXCR2 chemokines. Our data provide evidence for a suppressive immune microenvironment in patients with TRL and suggest promising targets, such as the CXCR2 axis, for its therapeutic intervention.

Validation and optimization of a web-based nomogram for predicting survival of patients with newly diagnosed glioblastoma.

PURPOSE: To optimize and validate a current (NRG [a newly constituted National Clinical Trials Network group through National Surgical Adjuvant Breast and Bowel Project [NSABP], the Radiation Therapy Oncology Group [RTOG] and the Gynecologic Oncology Group (GOG)]) nomogram for glioblastoma patients as part of continuous validation. METHODS: We identified patients newly diagnosed with glioblastoma who were treated with temozolomide-based chemoradiotherapy between 2006 and 2016 at three large-volume hospitals. The extent of resection was determined via postoperative MRI. The discrimination and calibration abilities of the prediction algorithm were assessed; if additional factors were identified as independent prognostic factors, updated models were developed using the data from two hospitals and were externally validated using the third hospital. Models were internally validated using cross-validation and bootstrapping. RESULTS: A total of 837 patients met the eligibility criteria. The median overall survival (OS) was 20.0 (95% CI 18.5-21.5) months. The original nomogram was able to estimate the 6­, 12-, and 24-month OS probabilities, but it slightly underestimated the OS values. In multivariable Cox regression analysis, MRI-defined total resection had a greater impact on OS than that shown by the original nomogram, and two additional factors-IDH1 mutation and tumor contacting subventricular zone-were newly identified as independent prognostic values. An updated nomogram incorporating these new variables outperformed the original nomogram (C-index at 6, 12, 24, and 36 months: 0.728, 0.688, 0.688, and 0.685, respectively) and was well calibrated. External validation using an independent cohort showed C­indices of 0.787, 0.751, 0.719, and 0.702 at 6, 12, 24, and 36 months, respectively, and was well calibrated. CONCLUSION: An updated and validated nomogram incorporating the contemporary parameters can estimate individual survival outcomes in patients with glioblastoma with better accuracy.

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

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

Diabetic polyneuropathy and the risk of developing carpal tunnel syndrome: A nationwide, population-based study.

BACKGROUND: We investigated the risk of carpal tunnel syndrome (CTS) in diabetic polyneuropathy (DPN). METHODS: This study was conducted using records from the National Health Insurance System (NHIS). We divided patients diagnosed with diabetes mellitus (DM) into those with and without DPN. We assessed the effect of DPN on the risk of CTS using Cox proportional hazards regression analyses. RESULTS: DPN was associated with an increased risk of CTS (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.12-1.58). In sub-analyses, female gender (HR, 1.45; 95% CI, 1.20-1.76), presence of type 2 DM (HR, 1.36; 95% CI, 1.11-1.64), and age 35 to 64 years (HR 1.35; 95% CI, 1.11-1.64) were significantly associated with an increased risk of CTS. CONCLUSIONS: Patients with DPN had an increased risk of CTS compared with the non-DPN group, particularly females, those with type 2 DM, and those aged 35 to 64 years.

Male sex and Breslow thickness are important risk factors for recurrence of localized melanoma in Korean populations.

BACKGROUND: Predicting the recurrence of localized melanoma is important; however, studies investigating risk factors for recurrence of localized melanoma are lacking in Asian populations. OBJECTIVE: To identify risk factors for recurrence of localized melanoma in Korean patients. METHODS: We retrospectively reviewed patients with cutaneous melanoma without evidence of metastasis from 2000 to 2017. Logistic and Cox regression analyses were conducted for recurrence. The average follow-up time was 46.2 months. RESULTS: We reviewed the data of 340 patients diagnosed with cutaneous melanoma and staged as melanoma in situ, stages I and II. Acral melanoma (70.3%, 239/340) was the predominant subtype. Ninety-two patients (27.1%) had a recurrence after primary melanoma removal (29 local recurrences, 49 regional metastases, and 28 distant metastases). Some patients had multiple types of recurrence at the same time. Male sex (P = .030) and Breslow thickness greater than 1 mm (P = .008) correlated with an increased risk of recurrence. Breslow thickness greater than 2.5 mm in males and greater than 4 mm in females showed a higher predictive value for recurrence than traditional stages IIB and IIC (hazard ratio 3.743 vs 2.972). LIMITATIONS: This was a single-center retrospective study. CONCLUSION: In patients with localized cutaneous melanoma, male sex and Breslow thickness are the most important prognostic factors for recurrence in Korean populations. Different cutoff values of Breslow thickness may better predict recurrence according to sex.

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

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

Involved-field radiation therapy for recurrent ovarian cancer: Results of a multi-institutional prospective phase II trial.

OBJECTIVE: To evaluate the efficacy and safety of involved-field radiation therapy (IFRT) in patients with locoregionally confined recurrent or persistent epithelial ovarian cancer. METHODS: This study included patients with recurrent epithelial ovarian cancer eligible for IFRT either during diagnosis of the recurrence or after salvage therapies. IFRT was performed at a dose of ≥45 Gy for all tumors with 10-15-mm margins as seen on standard imaging. The primary endpoint was progression-free survival (PFS); the secondary endpoints were safety, response rate, local control, and overall survival (OS). RESULTS: Thirty patients with a mean number of 5.7 metastatic lesions each were enrolled between 2014 and 2016. Seventeen were treated with 3-D conformal radiation therapy (RT) and 13 with intensity-modulated RT. IFRT was well tolerated in all patients, and acute toxicity ≥ grade 2 was not observed. One case of grade 3 abdominal pain was reported 10 months post-RT. The overall and complete response rates were 85.7% and 50%, respectively. After a median follow-up of 28 (range, 17-42) months, the median PFS was 7 months. The 2-year PFS rate was 39.3%. Six of the 16 patients who developed outfield disease progression after IFRT were successfully treated with repeat IFRT as salvage treatment. The 3-year local control and OS rates were 84.4% and 55.8%, respectively. CONCLUSIONS: Although the primary endpoint was not met, IFRT might be safe and effective for in-field tumor control in patients with persistent epithelial ovarian cancer with a limited number of metastatic foci. We plan to conduct a larger scale multi-center phase II prospective study.

Radiation-related heart disease after breast cancer radiation therapy in Korean women.

PURPOSE: To study the late cardiac toxicity of breast radiation therapy (RT) in Asian women. METHODS: Female breast cancer patients in Korea who underwent breast conservation surgery followed by RT from 1990-2012 were identified from two large registries at institution and population levels. Cumulative incidences of acute coronary events (ACE) or cardiac mortality were estimated in relation to the laterality of breast cancer using a competing risks analysis. RESULTS: In an analysis of 2577 women from a single institution, 3.7% were obese (body mass index ≥30), and 3.4% were ever-smokers. Patients with a history of hypertension, diabetes, or coronary artery disease were 17.5, 5.7, and 2.8%, respectively. The mean heart doses were 6.2 and 1.5 Gy for left- and right-sided tumors, respectively. With a median follow-up of 7 (range 1-23) years, the overall and breast cancer-specific survivals at 10 years were 94.9 and 96.5%, respectively. The 10-year cumulative incidence of ACE was 2.96%. The mean time to ACE was 5.2 ± 3.9 years (range 1-17). There was no clinically relevant difference in rates of ACE between left-sided and right-sided patients, with an adjusted hazard ratio of 1.16 (CI 0.59-2.29). An analysis of 24,235 women in a nationwide registry validated these negative findings with respect to cardiac mortality, with an adjusted hazard ratio of 1.52 (CI 0.37-6.25). Increasing age, a higher body mass index, and a history of hypertension or ischemic heart disease were identified as risk factors. CONCLUSIONS: Our findings reassure that excess risk from breast RT may be small in healthy women, most of who not smoke, weigh less, and have fewer risk factors. A validation using a larger data set of National Health Insurance Corporation is ongoing.

Recursive partition analysis of peritoneal and systemic recurrence in patients with gastric cancer who underwent D2 gastrectomy: Implications for neoadjuvant therapy consideration.

BACKGROUND AND OBJECTIVES: To classify patients with nonmetastatic advanced gastric cancer who underwent D2-gastrectomy into prognostic groups based on peritoneal and systemic recurrence risks. METHODS: Between 2004 and 2007, 1,090 patients with T3-4 or N+ gastric cancer were identified from our registry. Recurrence rates were estimated using a competing-risk analysis. Different prognostic groups were defined using recursive partitioning analysis (RPA). RESULTS: Median follow-up was 7 years. In the RPA-model for peritoneal recurrence risk, the initial node was split by T stage, indicating that differences between patients with T1-3 and T4 cancer were the greatest. The 5-year peritoneal recurrence rates for patients with T4 (n = 627) and T1-3 (n = 463) disease were 34.3% and 9.1%, respectively. N stage and neural invasion had an additive impact on high-risk patients. The RPA model for systemic relapse incorporated N stage alone and gave two terminal nodes: N0-2 (n = 721) and N3 (n = 369). The 5-year cumulative incidences were 7.7% and 24.5%, respectively. CONCLUSIONS: We proposed risk stratification models of peritoneal and systemic recurrence in patients undergoing D2-gastrectomy. This classification could be used for stratification protocols in future studies evaluating adjuvant therapies such as preoperative chemoradiotherapy. J. Surg. Oncol. 2016;114:859-864. © 2016 2016 Wiley Periodicals, Inc.