Prognostic role of pathologic status other than complete response after neoadjuvant therapy followed by surgery in esophageal squamous cell carcinoma.

BACKGROUND: This retrospective study was performed to investigate the survival differences according to the pathologic status after neoadjuvant chemotherapy followed by surgery in esophageal squamous cell carcinoma (ESCC), and to investigate whether current AJCC 8th ypStage can predict survival accurately. METHODS: Data of 563 patients who received neoadjuvant therapy and esophagectomy for ESCC between 1994 and 2018 were retrospectively reviewed. RESULTS: The mean age was 62.00 ± 8.01 years, of which 524 (93.1%) were males. The median follow-up period was 29.12 months. A total of 153 (27.1%) patients showed pathologic complete response (pCR) and 92 (16.3%) patients showed pCR of the primary lesion with residual metastatic lymph nodes (ypT0N +). A total of 196 (35%) and 122 (21.6%) patients showed ypT + N + and ypT + N, respectively. The 5-year overall survival (OS) of each group was 75.1% (CR), 42.4% (ypT + N0), 54.9% (ypT0N +), and 26.1% (ypT + N +); CR patients showed better survival than the other groups, and no survival differences were found in the 5-year OS between ypT + N0 and ypT0N + patients (p = 0.811). In ypStage I, there were survival differences between ypT0N0 and ypTis-2N0 patients, and ypT1N0 (ypStage I) and ypT0N1 (ypStageIIIA) showed similar OS (5-year OS in 49.3% vs. 67.1%, p = 0.623). CONCLUSIONS: pCR offers long-term survival in patients; however, survival significantly declines with the presence of residual primary lesion and nodal metastases.

Efficacy of the PRO-CTCAE mobile application for improving patient participation in symptom management during cancer treatment: a randomized controlled trial.

PURPOSE: Although mobile-based symptom monitoring is expected to improve patient participation in symptom management during anticancer therapy, previous trials have not evaluated its effectiveness. Therefore, this study aims to evaluate the impact of a symptom monitoring mobile application on improving patient participation in symptom management during anticancer therapy. METHODS: We conducted a single-center, open-label, randomized controlled trial that enrolled patients with breast, lung, head and neck, esophageal, or gynecologic cancer who were scheduled to receive anticancer therapy (oral or intravenous) between October 2020 and March 2021. We excluded patients with physical or psychological problems. The intervention group received a symptom monitoring application for 8 weeks, and the control group received the usual clinical practice. At 8 weeks, the improvement in patient participation in symptom management was assessed, and additionally quality of life and unplanned clinical visits were assessed. RESULTS: A total of 222 patients were included in the analysis, of whom 142 were randomly assigned to the intervention group and 71 to the control group. The intervention group reported better outcome in patient participation in symptom management than the control group at 8 weeks (mean scores of 8.5 vs. 8.0; P = 0.01). There were no significant differences between the groups in Quality of life (P = 0.88) and unplanned clinical visits (P = 0.39-0.76). CONCLUSIONS: This study is meaningful in figuring out that the mobile-based symptom monitoring made them more engaged in their management. Future research should continue to evaluate the effects of patient participation as mediators of clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04568278.

Durvalumab and tremelimumab with definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: The current standard treatment for patients with inoperable, locally advanced esophageal squamous cell carcinoma (ESCC) is definitive concurrent chemoradiotherapy (CCRT). METHODS: Patients with locally advanced ESCC received 2 cycles of 5-fluorouracil, cisplatin, durvalumab, and tremelimumab every 3 weeks with concurrent radiation therapy (60.2 or 64.5 grays). After completing CCRT plus immunotherapy, patients received 2 cycles of consolidative durvalumab and tremelimumab followed by durvalumab monotherapy every 4 weeks for 2 years after enrollment. Their survival outcomes were compared with those from a propensity score-matched historical control group that had received CCRT alone. RESULTS: In total, 40 patients were enrolled and analyzed. The 24-month progression-free survival (PFS) and overall survival rates were 57.5% and 75%, respectively. Compared with the historical control group (n = 75), the study population had significantly longer PFS (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.28-0.97; P = .040) and overall survival (HR, 0.49; 95% CI, 0.25-0.98; P = .043). In the study population, patients who had PD-L1-positive tumors (n = 28) had significantly longer PFS (HR, 0.20; 95% CI, 0.07-0.54; P < .001) and overall survival (HR, 0.16; 95% CI, 0.05-0.56; P = .001) compared with those who had PD-L1-negative tumors (n = 11). However, there was no difference in survival outcomes according to PD-L1 status in the historical control group, indicating a strong interaction between PD-L1-positive status and survival outcomes in the treatment groups (PFS, P for interaction = .003; overall survival, P for interaction = .002). CONCLUSIONS: Durvalumab and tremelimumab with definitive CCRT had promising efficacy in patients with locally advanced ESCC. In addition, PD-L1 expression had strong predictive value in the study population.

Trimodality therapy for locally advanced esophageal squamous cell carcinoma: the role of volume-based PET/CT in patient management and prognostication.

PURPOSE: To evaluate the role of positron emission tomography/computed tomography (PET/CT) in predicting pathologic complete response (pCR) and identify relevant prognostic factors from clinico-imaging-pathologic features of locally advanced esophageal squamous cell carcinoma (eSCC) patients undergoing trimodality therapy. METHODS: We evaluated 275 patients with eSCCs of T3-T4aN0M0 and T1-T4aN1-N3M0 who received trimodality therapy. We correlated volume-based PET/CT parameters before and after concurrent chemoradiation therapy with pCR after surgery, clinico-imaging-pathologic features, and patient survival. RESULTS: pCR occurred in 75 (27.3%) of 275 patients, of whom 61 (80.9%) showed 5-year survival. Pre-total lesion glycolysis (pre-TLG, OR = 0.318, 95% CI 0.169 to 0.600), post-metabolic tumor volume (post-MTV, OR = 0.572, 95% CI 0.327 to 0.999), and % decrease of average standardized uptake value (% SUVavg decrease, OR = 2.976, 95% CI = 1.608 to 5.507) were significant predictors for pCR. Among them, best predictor for pCR was pre-TLG with best cutoff value of 205.67 and with AUC value of 0.591. Performance status (HR = 5.171, 95% CI 1.737 to 15.397), pathologic tumor size (HR = 1.645, 95% CI 1.351 to 2.002), pathologic N status (N1, HR = 1.572, 95% CI 1.010 to 2.446; N2, HR = 3.088, 95% CI 1.845 to 5.166), and post-metabolic tumor volume (HR = 1.506, 95% CI 1.033 to 2.195) were significant predictors of overall survival. CONCLUSION: Pre-TLG, post-MTV, and % SUVavg decrease are predictive of pCR. Additionally, several clinico-imaging-pathologic factors are significant survival predictors in locally advanced eSCC patients undergoing trimodality therapy.

Who is more likely to adopt and comply with the electronic patient-reported outcome measure (ePROM) mobile application? A real-world study with cancer patients undergoing active treatment.

PURPOSE: This study aims to identify factors associated with the adoption and compliance of electronic patient-reported outcome measure (ePROM) use among cancer patients in a real-world setting. METHODS: This prospective cohort study was conducted at the Samsung Medical Center in Seoul, Korea, from September 2018 to January 2019. Cancer patients aged 18 years or older who owned smartphones and who were receiving chemotherapy or radiation therapy were eligible for this study. Patients were asked to use the app to report their symptoms every 7 days for a total of 21 days (3 weeks). Logistic regression was performed to identify the factors associated with the adoption and compliance. RESULTS: Among 580 patients, 417 (71.9%) adopted the ePROM app and 159 (27.4%) out of 417 had good compliance. Patients who had greater expectations regarding the ease of use (adjusted odds ratio [aOR] 2.67, 95% CI: 1.28-5.57) and usefulness (aOR 1.69, 95% CI: 1.05-2.72) of the ePROM app were more likely to adopt the app than those who did not. Patients who had greater satisfaction with usefulness (aOR 1.89, 95% CI 1.10-3.25) were more likely to comply with using the app, but satisfaction with ease of use was not related to the compliance. CONCLUSION: While expectation regarding the ease of use and usefulness of the ePROM app was associated with the adoption of the app, satisfaction with ease of use was not related to compliance with the ePROM app. Satisfaction with usefulness was associated with the compliance of ePROM app use.

High-Throughput 3D Tumor Spheroid Array Platform for Evaluating Sensitivity of Proton-Drug Combinations.

Proton beam therapy (PBT) is a critical treatment modality for head and neck squamous cell carcinoma (HNSCC). However, not much is known about drug combinations that may improve the efficacy of PBT. This study aimed to test the feasibility of a three-dimensional (3D) tumor-spheroid-based high-throughput screening platform that could assess cellular sensitivity against PBT. Spheroids of two HNSCC cell lines-Fadu and Cal27-cultured with a mixture of Matrigel were arrayed on a 384-pillar/well plate, followed by exposure to graded doses of protons or targeted drugs including olaparib at various concentrations. Calcein staining of HNSCC spheroids revealed a dose-dependent decrease in cell viability for proton irradiation or multiple targeted drugs, and provided quantitative data that discriminated the sensitivity between the two HNSCC cell lines. The combined effect of protons and olaparib was assessed by calculating the combination index from the survival rates of 4 × 4 matrices, showing that Cal27 spheroids had greater synergy with olaparib than Fadu spheroids. In contrast, adavosertib did not synergize with protons in both spheroids. Taken together, we demonstrated that the 3D pillar/well array platform was a useful tool that provided rapid, quantitative data for evaluating sensitivity to PBT and drug combinations. Our results further supported that administration of the combination of PBT and olaparib may be an effective treatment strategy for HNSCC patients.

Development and Validation of Digital Health Technology Literacy Assessment Questionnaire.

In clinical practice, assessing digital health literacy is important to identify patients who may encounter difficulties adapting to digital health using digital technology and service. We developed the Digital Health Technology Literacy Assessment Questionnaire (DHTL-AQ) to assess the ability to use digital health technology, services, and data. The DHTL-AQ was developed in three phases. In the first phase, the conceptual framework and domains and items were generated from a systematic literature review using relevant theory and surveys. In the second phase, a cross-sectional survey with 590 adults age ≥ 18 years was conducted at an academic hospital in Seoul, Korea in January and February 2020 to test face validity of the items. Then, psychometric validation was conducted to determine the final items and cut-off scores of the DHTL-AQ. The eHealth literacy scale, the Newest Vital Sign, and 10 mobile app task ability assessments were examined to test validity. The final DHTL-AQ includes 34 items in two domains (digital functional and digital critical literacy) and 4 categories (Information and Communications Technology terms, Information and Communications Technology icons, use of an app, evaluating reliability and relevance of health information). The DHTL-AQ had excellent internal consistency (overall Cronbach's α = 0.95; 0.87-0.94 for subtotals) and acceptable model fit (CFI = 0.821, TLI = 0.807, SRMR = 0.065, RMSEA = 0.090). The DHTL-AQ was highly correlated with task ability assessment (r = 0.7591), and moderately correlated with the eHealth literacy scale (r = 0.5265) and the Newest Vital Sign (r = 0.5929). The DHTL-AQ is a reliable and valid instrument to measure digital health technology literacy.

Feasibility of an Interactive Health Coaching Mobile App to Prevent Malnutrition and Muscle Loss in Esophageal Cancer Patients Receiving Neoadjuvant Concurrent Chemoradiotherapy: Prospective Pilot Study.

BACKGROUND: Excessive muscle loss is an important prognostic factor in esophageal cancer patients undergoing neoadjuvant chemoradiotherapy (NACRT), as reported in our previous research. OBJECTIVE: In this pilot study, we prospectively tested the feasibility of a health coaching mobile app for preventing malnutrition and muscle loss in this patient population. METHODS: Between July 2019 and May 2020, we enrolled 38 male patients with esophageal cancer scheduled for NACRT. For 8 weeks from the start of radiotherapy (RT), the patients used Noom, a health coaching mobile app that interactively provided online advice about food intake, exercise, and weight changes. The skeletal muscle index (SMI) measured based on computed tomography and nutrition-related laboratory markers were assessed before and after RT. We evaluated the changes in the SMI, nutrition, and inflammatory factors between the patient group that used the mobile app (mHealth group) and our previous study cohort (usual care group). Additionally, we analyzed the factors associated with walk steps recorded in the app. RESULTS: Two patients dropped out of the study (no app usage; treatment changed to a definitive aim). The use (or activation) of the app was noted in approximately 70% (25/36) of the patients until the end of the trial. Compared to the 1:2 matched usual care group by propensity scores balanced with their age, primary tumor location, tumor stage, pre-RT BMI, and pre-RT SMI level, 30 operable patients showed less aggravation of the prognostic nutritional index (PNI) (-6.7 vs -9.8; P=.04). However, there was no significant difference in the SMI change or the number of patients with excessive muscle loss (∆SMI/50 days >10%). In patients with excessive muscle loss, the walk steps significantly decreased in the last 4 weeks compared to those in the first 4 weeks. Age affected the absolute number of walk steps (P=.01), whereas pre-RT sarcopenia was related to the recovery of the reduced walk steps (P=.03). CONCLUSIONS: For esophageal cancer patients receiving NACRT, a health care mobile app helped nutritional self-care with less decrease in the PNI, although it did not prevent excessive muscle loss. An individualized care model with proper exercise as well as nutritional support may be required to reduce muscle loss and malnutrition.

Patient-Reported Outcomes Measurement Information System: Translation and Linguistic Validation of Six Profile Domains for Korean Adults.

BACKGROUND: The purpose of the study was to translate and linguistically validate a Korean language version of the PROMIS (K-PROMIS) for the six profile adult domains: Fatigue, Pain Intensity, Pain Interference, Physical Function, Sleep Disturbance, and Ability to Participate in Social Roles and Activities. METHODS: A total of 268 items were translated into Korean according to the Functional Assessment of Chronic Illness Therapy multilingual translation methodology. Participants first completed approximately 27 to 35 items and were then interviewed to evaluate the conceptual equivalence of the translation to the original English language source. The K-PROMIS items that met the a priori threshold of ≥ 20% of respondents with comprehension difficulties in the cognitive interview. RESULTS: 54 of the 268 items were identified as difficult items to comprehend for at least 20% of respondents in Round 1. The most frequently identified K-PROMIS domain on difficult items to comprehend was the Physical function (24.5%). Most items with linguistic difficulties were Fatigue and Physical function. Cultural difficulties were only included the Physical function and Ability to Participate in Social Roles and Activities domains. 25 of 54 items were slightly revised, and then these revised items were tested with additional six participants in Round 2, and most participants had no problems to understand modified items. CONCLUSION: The six profile adult domains of K-PROMIS have been linguistically validated. Further psychometric validation of the K-PROMIS items will provide additional information of meaningful outcomes for chronic disease and clinical setting.

Effect of photobiomodulation therapy on radiodermatitis in a mouse model: an experimental animal study.

This study aimed to evaluate the effect of photobiomodulation (PBM) for prevention of radiodermatitis in an irradiated mouse model and compare the efficacy of PBM using 633- or 830-nm wavelengths. Irradiated mice were randomly distributed into three groups: A (633 nm), B (830 nm), and C (without PBM). On post-irradiation days 7 and 21, we compared acute damage and recovery in treated skin samples to non-irradiated skin using H&E, Masson's trichrome, anti-CD45 and PCNA immunohistochemistry, and a TUNEL assay. Grade 3 radiodermatitis was evident only in group C. Compared with that in group C, the skin in groups A and B had significantly less epidermal hyperplasia, inflammatory cell infiltration, and thinner dermis on day 7 and less inflammatory cell infiltration, fewer apoptotic cells, and thinner dermis on day 21. However, there was no significant difference between groups A and B. This study indicates PBM could prevent severe radiodermatitis by reducing epidermal and dermal damage, inflammation, and apoptosis. There was no difference in PBM efficacy between the 633- and 830-nm wavelengths.

Feasibility of photobiomodulation therapy for the prevention of radiodermatitis: a single-institution pilot study.

Acute radiodermatitis is one of the major complications when radiation therapy (RT) is delivered to the head and neck region in cases of head and neck cancers or lung cancers with supraclavicular lymph node metastasis. In these cases, high dose of RT is generally used so that acute radiodermatitis is observed in more than 90% of patients, and it negatively affects patients' quality of life. In this pilot study, we evaluated the clinical feasibility of photobiomodulation (PBM) therapy before conducting a randomized trial based on the hypothesis that PBM therapy may reduce the severity of radiodermatitis in participants receiving 60 Gy or higher dose. Patients who were to receive 60 Gy or higher dose in the neck were included in the study. Thirty-three patients received PBM therapy three times a week during RT. The severity of radiodermatitis was evaluated by two dermatologists and a radiation oncologist using the modified Common Terminology Criteria for Adverse Events (CTCAE). Patients were followed up until a week after RT. In all patients, 90.6% of planned PBM schedule was completed. There was no significant side effect of PBM therapy. Thirteen (39%) patients showed wet desquamation (CTCAE grade 2b or higher). Only three (9%) of them showed grade 3 toxicity, which is a favorable result compared with previous studies. This pilot study showed that PBM therapy is safe and feasible in the clinic, and it might reduce the severity of radiodermatitis. A randomized trial should be warranted to prove the efficacy of PBM therapy.

Early clinical outcomes of helical tomotherapy/intensity-modulated proton therapy combination in nasopharynx cancer.

This study aimed to evaluate the feasibility of combining helical tomotherapy (HT) and intensity-modulated proton therapy (IMPT) in treating patients with nasopharynx cancer (NPC). From January 2016 to March 2018, 98 patients received definitive radiation therapy (RT) with concurrent chemotherapy (CCRT). Using simultaneous integrated boost and adaptive re-plan, 3 different dose levels were prescribed: 68.4 Gy in 30 parts to gross tumor volume (GTV), 60 Gy in 30 parts to high-risk clinical target volume (CTV), and 36 Gy in 18 parts to low-risk CTV. In all patients, the initial 18 fractions were delivered by HT, and, after rival plan evaluation on the adaptive re-plan, the later 12 fractions were delivered either by HT in 63 patients (64.3%, HT only) or IMPT in 35 patients (35.7%, HT/IMPT combination), respectively. Propensity-score matching was conducted to control differences in patient characteristics. In all patients, grade ≥ 2 mucositis (69.8% vs 45.7%, P = .019) and grade ≥ 2 analgesic usage (54% vs 37.1%, P = .110) were found to be less frequent in HT/IMPT group. In matched patients, grade ≥ 2 mucositis were still less frequent numerically in HT/IMPT group (62.9% vs 45.7%, P = .150). In univariate analysis, stage IV disease and larger GTV volume were associated with increased grade ≥ 2 mucositis. There was no significant factor in multivariate analysis. With the median 14 month follow-up, locoregional and distant failures occurred in 9 (9.2%) and 12 (12.2%) patients without difference by RT modality. In conclusion, comparable early oncologic outcomes with more favorable acute toxicity profiles were achievable by HT/IMPT combination in treating NPC patients.

Diagnostic value of surveillance 18F-fluorodeoxyglucose PET/CT for detecting recurrent esophageal carcinoma after curative treatment.

PURPOSE: Esophageal carcinoma recurs within two years in approximately half of patients who receive curative treatment and is associated with poor survival. While 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is a reliable method of detecting recurrent esophageal carcinoma, in most previous studies FDG PET/CT scans were performed when recurrence was suspected. The aim of this study was to evaluate FDG PET/CT as a surveillance modality to detect recurrence of esophageal carcinoma after curative treatment where clinical indications of recurrent disease are absent. METHODS: A total of 782 consecutive FDG PET/CT studies from 375 patients with esophageal carcinoma after definitive treatment were reviewed. Abnormal lesions suggestive of recurrence on PET/CT scans were then evaluated. Recurrence was determined by pathologic confirmation or other clinical evidence within two months of the scan. If no clinical evidence for recurrence was found at least 6 months after the scan, the case was considered a true negative for recurrence. RESULTS: The diagnostic sensitivity and specificity of PET/CT for detecting recurrent esophageal carcinomas were 100% (64/64) and 94.0% (675/718), respectively. There were no significant differences in the diagnostic performance of PET/CT for detecting recurrence according to initial stage or time between PET/CT and curative treatments. Unexpected second primary cancers were detected by FDG PET/CT in seven patients. CONCLUSIONS: Surveillance FDG PET/CT is a useful imaging tool for detection of early recurrence or clinically unsuspected early second primary cancer in patients with curatively treated esophageal carcinoma but without clinical suspicion of recurrence.

Prognostic impact of MYC protein expression in central nervous system diffuse large B-cell lymphoma: comparison with MYC rearrangement and MYC mRNA expression.

The prognostic role of MYC has been well documented in non-central nervous system diffuse large B-cell lymphoma; however, it remains controversial in central nervous system diffuse large B-cell lymphoma. To investigate the prognostic value of MYC, we analyzed the MYC protein expression by immunohistochemistry, mRNA expression by RNA in situ hybridization, and gene status by fluorescence in situ hybridization in 74 cases of central nervous system diffuse large B-cell lymphoma. Moreover, we examined the correlation between MYC translocation, mRNA expression, and protein expression. The mean percentage of MYC immunopositive cells was 49%. Using a 44% cutoff value, 49 (66%) cases showed MYC protein overexpression. The result of mRNA in situ hybridization using the RNA scope technology was obtained using the H-scoring system; the median value was 34.2. Using the cutoff value of 63.5, 16 (22%) cases showed MYC mRNA overexpression. MYC gene rearrangement was detected in five out of 68 (7%) cases. MYC translocation showed no statistically significant correlation with mRNA expression; however, all MYC translocation-positive cases showed MYC protein overexpression, with a higher mean percentage of MYC protein expression than that of translocation-negative cases (78 vs 48%, P=0.001). The level of MYC mRNA expression was moderately correlated with the level of MYC protein expression (P<0.001). The mean percentage of MYC protein expression in the high MYC mRNA group was higher than that in the low MYC mRNA group (70 vs 47%, P<0.001). A univariate analysis showed that age over 60 years, Eastern Cooperative Oncology Group (ECOG) performance status ≥2 and MYC protein overexpression were significantly associated with an increased risk of death. MYC translocation and MYC mRNA expression had no prognostic significance. On multivariate analysis, MYC protein overexpression and ECOG score retained prognostic significance.

Chemoradiotherapy versus surgery followed by postoperative radiotherapy in tonsil cancer: Korean Radiation Oncology Group (KROG) study.

BACKGROUND: Treatment of tonsil cancer, a subset of oropahryngeal cancer, varies between surgery and radiotherapy. Well-designed studies in tonsil cancer have been rare and it is still controversial which treatment is optimal. This study aimed to assess the outcome and failure patterns in tonsil cancer patients treated with either approaches. METHODS: We retrospectively reviewed medical records of 586 patients with tonsil cancer, treated between 1998 and 2010 at 16 hospitals in Korea. Two hundred and one patients received radiotherapy and chemotherapy (CRT), while 385 patients received surgery followed by radiotherapy and/or chemotherapy (SRT). Compared with the SRT group, patients receiving CRT were older, with more advanced T stage and received higher radiotherapy dose given by intensity modulation techniques. Overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and clinicopathologic factors were analyzed. RESULTS: At follow-up, the 5-year OS, DFS, LRRFS and DMFS rates in the CRT group were 82, 78, 89, and 94%, respectively, and in the SRT group were 81, 73, 87, and 89%, respectively. Old age, current smoking, poor performance status, advanced T stage, nodal involvement, and induction chemotherapy were associated with poor OS. Induction chemotherapy had a negative prognostic impact on OS in both treatment groups (p = 0.001 and p = 0.033 in the CRT and SRT groups, respectively). CONCLUSIONS: In our multicenter, retrospective study of tonsil cancer patients, the combined use of radiotherapy and chemotherapy resulted in comparable oncologic outcome to surgery followed by postoperative radiotherapy, despite higher-risk patients having been treated with the definitive radiotherapy. Induction chemotherapy approaches combined with either surgery or definitive radiotherapy were associated with unfavorable outcomes.

Role of radiation therapy in primary central nervous system lymphoma : KROG 14-20 Collaborative Study of Brain and Lymphoma Committee.

We analyzed patterns of care and outcomes for patients with primary central nervous system lymphoma (PCNSL) in this multi-institutional retrospective study. Between January 2000 and December 2011, 220 patients with PCNSL received radiotherapy (RT). Among these patients, 26 patients received RT alone; 179 patients were treated with chemotherapy and radiotherapy; the rest of the patients (N = 15) initially underwent chemotherapy alone, then received RT as a salvage treatment. Most of the patients (N = 188) received methotrexate-based chemotherapy. The median follow up duration was 38 months (range 3-179 months). The median RT dose and whole brain RT (WBRT) dose were 45.0 Gy (range 20.0-59.4) and 30.6 Gy (range 18.0-45.0), respectively. Seventy-seven (35%) patients received WBRT alone, and 143 patients (65%) underwent WBRT plus boost RT. Total RT dose and WBRT dose decreased during the study period. The median survival was 64 months and actuarial 5-year overall survival was 51.4%. In multivariate analysis, age (P < 0.001), ECOG performance status (P = 0.036), deep structure involvement (P = 0.011) and treatment response (P = 0.001) were significant prognosticators. RT combined with chemotherapy is effective modality for treatment of PCNSL. The survival outcome improved in spite of total radiation dose and whole brain RT (WBRT) dose having been decreased over the study period, indicating that low-dose WBRT could be effective.

Comparison of Oncological and Functional Outcomes between Initial Surgical versus Non-Surgical Treatments for Hypopharyngeal Cancer.

BACKGROUND: Whether to administer surgical or non-surgical treatments (radiation or chemoradiation therapies) for the initial management of hypopharyngeal cancer (HPC) remains a topic of debate. Herein, we explored the differences between the two approaches in terms of oncological and functional outcomes in 332 HPC patients. METHODS: The primary endpoint was survival probability; secondary outcomes included post-treatment speech and swallowing functions and necessity of additional surgical procedures for salvage or complication management. Cox proportional hazard models using clinical variables were constructed to identify significant factors. RESULTS: The 2- and 5-year overall survival (OS) rates in all patients were 64.9 and 40.9 %, respectively. In early-stage HPC patients (N = 52), initial surgery ± radiation therapy (RT) or RT alone yielded similar oncological (60 % 5-year OS rate) and functional outcomes. As for resectable advanced-stage cancers (N = 177), initial surgery ± RT/chemoradiation therapy (SRC) and initial concurrent chemoradiation therapy (iCRT) resulted in similar 45-50 % 5-year OS rates. After sacrificing the larynx, 60 % of SRC patients recovered their speaking ability through voice prosthesis, which was less than the rate for iCRT patients (76.6 %; p = 0.008). Additional surgical interventions were required in 28.0-28.6 % of patients in both groups; however, 60 % of patients undergoing additional surgery in the iCRT group received multiple (two or more) surgical interventions (p = 0.029). CONCLUSIONS: Our data revealed similar oncological outcomes, but different functional outcomes, between initial surgical and non-surgical treatments for HPC. In resectable advanced-stage HPC, iCRT resulted in better verbal communication outcomes than SRC; however, more iCRT patients required multiple surgical interventions during clinical courses.

Low-Grade Salivary Gland Cancers: Treatment Outcomes, Extent of Surgery and Indications for Postoperative Adjuvant Radiation Therapy.

BACKGROUND: Histologic grade of tumor is one of the major prognostic predictors for patients with salivary gland cancer. Because of disease rarity, little is known about the optimal treatment modalities and outcomes in low-grade salivary gland cancers (LGSGC). We tried to identify prognostic factors, and the adequate treatment modalities and outcomes in pathologically confirmed LGSGC patients. METHODS: We retrospectively extracted the clinical and pathology data from 179 LGSGC cases from 1995 to 2013. Pathological features, such as extraparenchymal extension, perineural/nerve invasion, lymphovascular invasion/tumor emboli, and resection margin status were redefined for each case. Risk factors for recurrence, extent of surgery, and the role of postoperative radiation therapy were analyzed. RESULTS: Recurrence-free survival and overall survival were 89.6 and 96.6 % at 10 years, respectively. The presence of regional nodal metastasis and positive cancer cells at resection margin were significant unfavorable prognostic factors. Postoperative adjuvant radiation treatment significantly reduced recurrences, particularly in cases with pathology risk factors (perineural invasion, lymphovascular invasion, extraparenchymal extension, or cancer cells at the resection margin), node metastasis, and advanced T-stage tumors. Close surgical margin <5 mm was not a significant risk factor for recurrence, and less-than-total resection of the affected gland did not increase recurrence, if surgery could achieve a cancer cell-free surgical margin. CONCLUSION: Postoperative radiation clearly benefitted patients with pathology risk factors, node metastasis, and advanced T stage in LGSGC. Meanwhile, the oncological outcomes are very good with surgery alone in cases of pT1-2N0 LGSGC without pathology risk factors.

IMRT vs. 2D-radiotherapy or 3D-conformal radiotherapy of nasopharyngeal carcinoma : Survival outcome in a Korean multi-institutional retrospective study (KROG 11-06).

OBJECTIVE: We compared treatment outcomes of two-dimensional radiotherapy (2D-RT), three-dimensional conformal radiotherapy (3D-CRT), and intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: In total, 1237 patients with cT1-4N0-3M0 NPC were retrospectively analyzed. Of these, 350, 390, and 497 were treated with 2D-RT, 3D-CRT, and IMRT, respectively. RESULTS: 3D-CRT and IMRT showed better 5-year overall survival (OS) rates (73.6 and 76.7 %, respectively) than did 2D-RT (5-year OS of 59.7 %, all p < 0.001). In T3-4 subgroup, IMRT was associated with a significantly better 5-year OS than was 2D-RT (70.7 vs. 50.4 %, respectively; p ≤ 0.001) and 3D-CRT (70.7 vs. 57.8 %, respectively; p = 0.011); however, the difference between the 2D-RT and 3D-CRT groups did not reach statistical significance (p = 0.063). In multivariate analyses of all patients, IMRT was a predictive factor for OS when compared with 2D-RT or 3D-CRT, as was 3D-CRT when compared with 2D-RT. CONCLUSION: Our study showed that 3D-CRT and IMRT were associated with a better local progression-free survival and OS than was 2D-RT in NPC. IMRT was significantly superior in terms of OS for advanced primary tumors (T3-4).

Combination treatment of trans-arterial chemo-embolisation, radiotherapy and hyperthermia (CERT) for hepatocellular carcinoma with portal vein tumour thrombosis: Interim analysis of prospective phase II trial.

Objectives This study evaluated the objective response to and toxicity of trans-arterial chemo-embolisation (TACE) followed by radiotherapy and hyperthermia (CERT) in hepatocellular carcinoma patients with portal vein tumour thrombosis. Methods The study design was a single-centre prospective phase II trial. Patients were first treated with TACE, with the first hyperthermia session 1 week later. Respiration-gated radiotherapy (RT) was delivered in 10 fractions of 3-5 Gy after another week. Six sessions of hyperthermia were delivered twice a week according to an energy escalation protocol. Response evaluation was planned at 1 month after RT completion using the modified Response Evaluation Criteria in Solid Tumors (RECIST). Toxicity was determined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results Interim analysis was conducted on patients enrolled from October 2013 to November 2014. During this period, 46 patients (90.2%) who received at least one hyperthermia session were eligible and enrolled. Median follow-up was 6.7 months (range 2.0-15.0 months). Complete response was observed in 10 (21.7%) patients and partial response in 27 (47.8%). Most toxicities were grade I or II. One death was related to severe pneumonia of unknown cause in the left lung and one patient could not complete planned treatment because of continuous elevation of bilirubin after TACE. Late, asymptomatic gastroduodenal toxicities were noticed in 13 (28.3%) patients. Conclusion Preliminary evaluation of CERT showed a promising response rate with acceptable toxicities.