MRI radiomics may predict early tumor recurrence in patients with sinonasal squamous cell carcinoma.

OBJECTIVES: Sinonasal squamous cell carcinoma (SCC) follows a poor prognosis with high tendency for local recurrence. We aimed to evaluate whether MRI radiomics can predict early local failure in sinonasal SCC. METHODS: Sixty-eight consecutive patients with node-negative sinonasal SCC (January 2005-December 2020) were enrolled, allocated to the training (n = 47) and test sets (n = 21). Early local failure, which occurred within 12 months of completion of initial treatment, was the primary endpoint. For clinical features (age, location, treatment modality, and clinical T stage), binary logistic regression analysis was performed. For 186 extracted radiomic features, different feature selections and classifiers were combined to create two prediction models: (1) a pure radiomics model; and (2) a combined model with clinical features and radiomics. The areas under the receiver operating characteristic curves (AUCs) were calculated and compared using DeLong's method. RESULTS: Early local failure occurred in 38.3% (18/47) and 23.8% (5/21) in the training and test sets, respectively. We identified several radiomic features which were strongly associated with early local failure. In the test set, both the best-performing radiomics model and the combined model (clinical + radiomic features) yielded higher AUCs compared to the clinical model (AUC, 0.838 vs. 0.438, p = 0.020; 0.850 vs. 0.438, p = 0.016, respectively). The performances of the best-performing radiomics model and the combined model did not differ significantly (AUC, 0.838 vs. 0.850, p = 0.904). CONCLUSION: MRI radiomics integrated with a machine learning classifier may predict early local failure in patients with sinonasal SCC. CLINICAL RELEVANCE STATEMENT: MRI radiomics intergrated with machine learning classifiers may predict early local failure in sinonasal squamous cell carcinomas more accurately than the clinical model. KEY POINTS: • A subset of radiomic features which showed significant association with early local failure in patients with sinonasal squamous cell carcinomas was identified. • MRI radiomics integrated with machine learning classifiers can predict early local failure with high accuracy, which was validated in the test set (area under the curve = 0.838). • The combined clinical and radiomics model yielded superior performance for early local failure prediction compared to that of the radiomics (area under the curve 0.850 vs. 0.838 in the test set), without a statistically significant difference.

Role of postoperative radiotherapy in resected adenoid cystic carcinoma of the head and neck.

PURPOSE: Although postoperative radiotherapy (PORT) is demonstrably effective in local control of head and neck adenoid cystic carcinoma (HNACC), its application is controversial and the subset of patients who would benefit most from PORT is unknown. Herein, we analyzed the data of HNACC patients to clarify the role of PORT. METHODS: We retrospectively reviewed 187 patients with nonmetastatic HNACC who underwent surgical resection between 2005 and 2019. The study endpoints were locoregional failure-free survival (LRFFS), progression-free survival (PFS), and overall survival (OS). Subgroup analysis and recursive partitioning analysis (RPA) were performed to identify patients most likely to benefit from PORT. RESULTS: With a median follow-up of 84.7 months, the 5-year LRFFS, PFS, and OS were 70.0%, 52.6%, and 86.4%, respectively. Survival was significantly shorter in patients who experienced local failure than in those who did not (5-year OS: 88.1% vs. 80.5%, P = 0.001). The local failure rate was significantly lower in patients who underwent PORT (16.9% vs. 31.0%, P = 0.021), despite the high frequency of adverse factors. Especially, significant decreases in local failure and similar OS rates could be obtained after PORT among patients with positive margins, T2-4 stage disease, and minor salivary gland tumors. The RPA model for PFS categorized patients into four groups according to three prognostic factors (T-stage, location, and sex). The RPA model for LRFFS and OS suggested three groups based on two factors (T-stage, margin for LRFFS; T-stage, grade 3 for OS). CONCLUSION: PORT could prevent dismal survival, while significantly reducing local failures in high-risk HNACC patients.

Treatment outcomes and radiotherapy deintensification strategies in human papillomavirus-associated tonsil cancer.

BACKGROUND: Human papillomavirus (HPV)-positive tonsil cancer has a better prognosis than HPV-negative tonsil cancer. Deintensification strategies to reduce or avoid radiotherapy (RT) for patients with HPV-associated tonsil cancer have been suggested. This study investigated the treatment outcomes of patients with HPV-associated tonsil cancer and suggested RT deintensification strategies. METHODS: A cohort of 374 patients with HPV-associated tonsil cancer treated with primary surgery or RT between 2008 and 2020 was retrospectively evaluated. Survival and locoregional control rates after primary surgery or RT were analyzed, and propensity score matching was performed to adjust for clinical factors. Pearson's chi-square or Fisher's exact test was used to compare categorical variables, and Student's t-test was used to compare continuous variables. The Kaplan-Meier method and log-rank test were used to assess overall survival, progression-free survival, and locoregional failure (LRF). RESULTS: No significant differences in survival or LRF were observed between the primary surgery and RT groups. Subgroup analysis was conducted for patients who underwent primary surgery. Advanced pathological N stage, negative contralateral nodes at diagnosis, abutting or positive surgical margins, and no adjuvant RT were independent risk factors for LRF. Advanced pathological T stage was an independent risk factor for LRF in patients who underwent primary surgery without subsequent adjuvant RT. None of the patients with pathological complete remission (CR) after induction chemotherapy died or experienced LRF. CONCLUSIONS: Our study revealed that the outcomes of primary surgery and primary RT in HPV-positive tonsil cancer were similar after adjusting for clinical factors. Primary RT might be considered instead of surgery in patients with advanced pathological T stage. In the case of pathological CR after induction chemotherapy, deintensification for adjuvant RT should be considered.

Postoperative Concurrent Chemoradiotherapy Versus Radiotherapy Alone for Advanced Oral Cavity Cancer in the Era of Modern Radiation Techniques.

BACKGROUND/PURPOSE: Surgery followed by postoperative radiotherapy (RT) has been considered the standard treatment for oral cavity squamous cell carcinoma (OCSCC) of advanced stages or with adverse prognostic factors. In this study, we compared the outcomes in patients with OCSCC who received postoperative concurrent chemoradiotherapy (CCRT) or postoperative RT alone using modern RT techniques. METHODS: A total of 275 patients with OCSCC treated between 2002 and 2018 were retrospectively analyzed. Adverse prognostic factor was defined as extranodal extension (ENE), microscopically involved surgical margin, involvement of ≥2 lymph nodes, perineural disease, and/or lymphovascular invasion (LVI). In total, 148 patients (54%) received CCRT and 127 patients (46%) received RT alone. More patients in the CCRT group had N3 disease and stage IVB disease (46.6% vs. 10.2%, p<0.001), ENE (56.1% vs. 15.7%, p<0.001), LVI (28.4% vs. 13.4%, p=0.033). RESULTS: With a median follow-up of 40 (range, 5-203) months, there were no significant differences in the 5-year overall survival (OS) and PFS between treatment groups. In the subgroup analysis according to high risk, the concurrent use of chemotherapy showed significantly improved OS in patients with ENE (HR 0.39, p=0.003). CONCLUSION: Our retrospective study showed that postoperative CCRT group had comparable survival outcomes to those in the RT alone group for advanced OCSCC in the era of modern RT techniques and indicated that concurrent chemotherapy should be administered to patients with ENE. Prospective randomized studies for confirmation are needed.

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.

Feasibility of Continual Deep Learning-Based Segmentation for Personalized Adaptive Radiation Therapy in Head and Neck Area.

This study investigated the feasibility of deep learning-based segmentation (DLS) and continual training for adaptive radiotherapy (RT) of head and neck (H&N) cancer. One-hundred patients treated with definitive RT were included. Based on 23 organs-at-risk (OARs) manually segmented in initial planning computed tomography (CT), modified FC-DenseNet was trained for DLS: (i) using data obtained from 60 patients, with 20 matched patients in the test set (DLSm); (ii) using data obtained from 60 identical patients with 20 unmatched patients in the test set (DLSu). Manually contoured OARs in adaptive planning CT for independent 20 patients were provided as test sets. Deformable image registration (DIR) was also performed. All 23 OARs were compared using quantitative measurements, and nine OARs were also evaluated via subjective assessment from 26 observers using the Turing test. DLSm achieved better performance than both DLSu and DIR (mean Dice similarity coefficient; 0.83 vs. 0.80 vs. 0.70), mainly for glandular structures, whose volume significantly reduced during RT. Based on subjective measurements, DLS is often perceived as a human (49.2%). Furthermore, DLSm is preferred over DLSu (67.2%) and DIR (96.7%), with a similar rate of required revision to that of manual segmentation (28.0% vs. 29.7%). In conclusion, DLS was effective and preferred over DIR. Additionally, continual DLS training is required for an effective optimization and robustness in personalized adaptive RT.

Clinical feasibility of deep learning-based auto-segmentation of target volumes and organs-at-risk in breast cancer patients after breast-conserving surgery.

BACKGROUND: In breast cancer patients receiving radiotherapy (RT), accurate target delineation and reduction of radiation doses to the nearby normal organs is important. However, manual clinical target volume (CTV) and organs-at-risk (OARs) segmentation for treatment planning increases physicians' workload and inter-physician variability considerably. In this study, we evaluated the potential benefits of deep learning-based auto-segmented contours by comparing them to manually delineated contours for breast cancer patients. METHODS: CTVs for bilateral breasts, regional lymph nodes, and OARs (including the heart, lungs, esophagus, spinal cord, and thyroid) were manually delineated on planning computed tomography scans of 111 breast cancer patients who received breast-conserving surgery. Subsequently, a two-stage convolutional neural network algorithm was used. Quantitative metrics, including the Dice similarity coefficient (DSC) and 95% Hausdorff distance, and qualitative scoring by two panels from 10 institutions were used for analysis. Inter-observer variability and delineation time were assessed; furthermore, dose-volume histograms and dosimetric parameters were also analyzed using another set of patient data. RESULTS: The correlation between the auto-segmented and manual contours was acceptable for OARs, with a mean DSC higher than 0.80 for all OARs. In addition, the CTVs showed favorable results, with mean DSCs higher than 0.70 for all breast and regional lymph node CTVs. Furthermore, qualitative subjective scoring showed that the results were acceptable for all CTVs and OARs, with a median score of at least 8 (possible range: 0-10) for (1) the differences between manual and auto-segmented contours and (2) the extent to which auto-segmentation would assist physicians in clinical practice. The differences in dosimetric parameters between the auto-segmented and manual contours were minimal. CONCLUSIONS: The feasibility of deep learning-based auto-segmentation in breast RT planning was demonstrated. Although deep learning-based auto-segmentation cannot be a substitute for radiation oncologists, it is a useful tool with excellent potential in assisting radiation oncologists in the future. Trial registration Retrospectively registered.

Risk of Cardiac Disease in Patients With Breast Cancer: Impact of Patient-Specific Factors and Individual Heart Dose From Three-Dimensional Radiation Therapy Planning.

PURPOSE: This retrospective cohort study aimed to determine whether adjuvant radiation therapy increases the risk of cardiac toxicity in Asian women with breast cancer, with a focus on patient-specific factors. METHODS AND MATERIALS: We evaluated women who underwent primary breast surgery for breast cancer with (n = 520) or without (n = 774) adjuvant radiation therapy between January 2005 and May 2013. Patients who underwent breast surgery without radiation therapy were categorized as patients who received 0 Gy to the heart. The primary endpoint was the occurrence of a breast cancer treatment-related heart disease (BCT-HD), defined as a diagnosis of angina pectoris, unstable angina, myocardial infarction, ischemic heart disease, heart failure, or atrial fibrillation. RESULTS: In total, 1294 patients were included. The overall 5- and 10-year BCT-HD rates were 2.4% and 5.7%, respectively. The risk of an BCT-HD significantly increased per 1-Gy increase in the mean heart dose (adjusted hazard ratio: 1.23). Additionally, histories of hypertension (hazard ratio: 1.92), and diabetes (hazard ratio: 2.51) were found to be adverse risk factors, whereas regular physical exercise (hazard ratio: 0.17) was a protective factor. Subgroup analysis according to risk groups showed that the effect of increasing mean heart dose (per Gy) was similar between women without or with minimal risk factors (hazard ratio: 1.23) and women with multiple risk factors (hazard ratio: 1.27). CONCLUSIONS: The results indicate a radiation dose-effect relationship for cardiac disease in breast cancer patients, highlighting that there remains a considerable risk of cardiac toxicity even with 3-dimensional radiation therapy planning. Thus, measures to minimize the heart dose in breast cancer patients undergoing adjuvant radiation therapy, even in those without any risk factor for cardiac disease, should be routinely implemented.

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.

Image quality of 4D in-treatment CBCT acquired during lung SBRT using FFF beam: a phantom study.

BACKGROUND: Rotational beam delivery enables concurrent acquisition of cone-beam CT (CBCT), thereby facilitating further geometric verification of patient setup during radiation treatment. However, it is challenging to acquire CBCT during stereotactic body radiation therapy (SBRT) using flattening-filter free X-ray beams, in which a high radiation dose is delivered. This study presents quantitative evaluation results of the image quality in four-dimensional (4D) in-treatment CBCT acquired during SBRT delivery. METHODS: The impact of megavoltage (MV) scatter and acquisition parameters on the image quality was evaluated using Catphan 503 and XSight lung tracking phantoms. The in-treatment CBCT images of the phantoms were acquired while delivering 16 SBRT plans. The uniformity, contrast, and contrast-to-noise ratio (CNR) of the in-treatment CBCT images were calculated and compared to those of CBCT images acquired without SBRT delivery. Furthermore, the localizing accuracy of the moving target in the XSight lung phantom was evaluated for 10 respiratory phases. RESULTS: The CNR of the 3D-reconstucted Catphan CBCT images was reduced from 6.3 to 2.6 due to the effect of MV treatment scatter. Both for the Catphan and XSight phantoms, the CBCT image quality was affected by the tube current and monitor units (MUs) of the treatment plan. The lung target in the XSight tracking phantom was most visible for extreme phases; the mean CNRs of the lung target in the in-treatment CBCT images (with 40 mA tube current) across the SBRT plans were 3.2 for the end-of-exhalation phase and 3.0 for the end-of-inhalation phase. The lung target was localized with sub-millimeter accuracy for the extreme respiratory phases. CONCLUSIONS: Full-arc acquisition with an increased tube current (e.g. 40 mA) is recommended to compensate for degradation in the CBCT image quality due to unflattened MV beam scatter. Acquiring in-treatment CBCT with a high-MU treatment beam is also suggested to improve the resulting CBCT image quality.

Hypofractionated Radiotherapy Dose Scheme and Application of New Techniques Are Associated to a Lower Incidence of Radiation Pneumonitis in Breast Cancer Patients.

Purpose: Radiation pneumonitis (RP) is one of the most severe toxicities experienced by patients with breast cancer after radiotherapy (RT). RT fractionation schemes and techniques for breast cancer have undergone numerous changes over the past decades. This study aimed to investigate the incidence of RP as a function of such changes in patients with breast cancer undergoing RT and to identify dosimetric markers that predict the risk of this adverse event. Methods and Materials: We identified 1,847 women with breast cancer who received adjuvant RT at our institution between 2015 and 2017. The RT technique was individually tailored based on each patient's clinicopathological features. Deep inspiration breath hold technique or prone positioning were used for patients who underwent left whole-breast irradiation for cardiac sparing, while those requiring regional lymph node irradiation underwent volumetric-modulated arc therapy (VMAT). Results: Of 1,847 patients who received RT, 21.2% received the conventional dose scheme, while 78.8% received the hypofractionated dose scheme (mostly 40 Gy in 15 fractions). The median follow-up period was 14.5 months, and the overall RP rate was 2.1%. The irradiated organ at risk was corrected concerning biologically equivalent dose. The ipsilateral lung V30 in equivalent dose in 2 Gy (EQD2) was the most significant dosimetric factor associated with RP development. Administering RT using VMAT, and hypofractionated dose scheme significantly reduced ipsilateral lung V30. Conclusions: Application of new RT techniques and hypofractionated scheme significantly reduce the ipsilateral lung dose. Our data demonstrated that ipsilateral lung V30 in EQD2 is the most relevant dosimetric predictor of RP in patients with breast cancer.

Patterns of local recurrence after curative resection and reconstruction for oropharyngeal and oral cancers: Implications for postoperative radiotherapy target volumes.

BACKGROUND: We aimed to determine the patterns of local recurrence after curative resection and reconstruction for oropharyngeal and oral cancers. METHODS: One hundred-fourteen patients with oropharyngeal and oral cancers underwent resection and reconstruction. The local recurrences were classified as "intra-flap" (the recurrent tumor was located in the flap tissue), "marginal" (≤5 mm from the flap anastomosis), and "outside" (in the original tissue and >5 mm from the anastomosis) recurrences. RESULTS: Twenty-seven patients (23.7%) experienced local recurrence, while 32 (28.1%) experienced regional, and nine (7.9%) recurred distantly. Among those who showed local recurrence, one developed "outside" recurrence and the remaining 26 developed "marginal" recurrences. Age >60 years and lymph node metastasis were associated with poor disease-free survival and overall survival (OS), while the perineural invasion was related to poor locoregional failure-free survival and OS. CONCLUSION: Most recurrences developed at the anastomosis marginal site, while none developed in the flap tissue.

Treatment Outcomes of Re-irradiation in Locoregionally Recurrent Rectal Cancer and Clinical Significance of Proper Patient Selection.

Background and Purpose: Majority of patients with locoregionally recurrent rectal cancer will require re-irradation (reRT). This study aimed to analyze the treatment outcomes, particularly infield progression, and severe late toxicity rates after reRT for recurrent rectal cancer and further identify a subgroup of patients who may optimally benefit from reRT. Materials and Methods: Patients with rectal cancer who underwent reRT to the pelvis between January 2000 and December 2017 were included for analysis. Results: The records of 41 patients were retrospectively reviewed. The median follow-up period after reRT was 53.7 months (range 3.5-130.3 months). The 2-year infield progression-free rate (IPFR) was 49.4%. The 2-year overall survival (OS) and progression-free survival (PFS) rates were 55.3 and 28.5%, respectively. Severe late toxicity events occurred in 17 patients, and the median time from reRT to severe late toxicity event was 10.5 months (range 2.3-33.3 months). The 2-year severe late toxicity free-rate (SLTFR) was 55.5%, and the median SLTFR was 33.3 months. Patients who did not experience severe late toxicity events showed a significantly higher number of recurred tumors at the posterior or lateral location compared to axial or anterior location. The selected subgroup with recurrent tumor size <3.3 cm and treated with total reRT dose of >50 Gyab10 (n = 13) showed superior IPFR, OS, and PFS to the other patients. Conclusion: ReRT was a reasonable treatment option for patients with locoregionally recurrent rectal cancer. However, severe late toxicity rates were substantially high. Thus, patients indicated for ReRT with curative dose should be selected properly according to tumor size and location.

Radiotherapy for initial clinically positive internal mammary nodes in breast cancer.

PURPOSE: Internal mammary lymph node (IMN) involvement is associated with poor prognosis in breast cancer. This study investigated the treatment outcomes of initial clinically IMN-positive breast cancer patients who received adjuvant radiotherapy (RT), including IMN irradiation, following primary breast surgery. MATERIALS AND METHODS: We retrospectively reviewed data of 95 breast cancer patients with clinically detected IMNs at diagnosis treated with surgery and RT between June 2009 and December 2015. Patients received adjuvant RT to the whole breast/chest wall and regional lymph node (axillary, internal mammary, and supraclavicular) areas. Twelve patients received an additional boost to the IMN area. RESULTS: The median follow-up was 43.2 months (range, 4.5 to 100.5 months). Among 77 patients who received neoadjuvant chemotherapy, 52 (67.5%) showed IMN normalization and 19 (24.6%) showed a partial response to IMN. There were 3 and 24 cases of IMN failure and any recurrence, respectively. The 5-year IMN failure-free survival, disease-free survival (DFS), and overall survival (OS) were 96%, 70%, and 84%, respectively. IMN failure-free survival was significantly affected by resection margin status (97.7% if negative, 87.5% for close or positive margins; p = 0.009). All three patients with IMN failure had initial IMN size ≥1 cm and did not receive IMN boost irradiation. The median age of the three patients was 31 years, and all had hormone receptor-negative tumors. CONCLUSION: RT provides excellent IMN control without the support of IMN surgery. Intensity-modulated radiotherapy, including IMN boost for breast cancer patients, is a safe and effective technique for regional lymph node irradiation.

Influence of Radiation Dose to Reconstructed Breast Following Mastectomy on Complication in Breast Cancer Patients Undergoing Two-Stage Prosthetic Breast Reconstruction.

Purpose: This study investigated the association between radiation dose and complication rate in patients who underwent breast reconstruction to understand the role of radiation hypofractionated regimen, boost radiation therapy (RT), and RT techniques. Methods: We retrospectively evaluated 75 patients treated with post-mastectomy adjuvant RT for breast cancer in the setting of two-stage prosthetic breast reconstruction. Near maximum radiation dose (Dmax) in the 2 or 0.03 cc of reconstructed breast or overlying breast skin was obtained from dose-volume histograms. Results: Post-RT complications occurred in 22.7% of patients. Receiver operating characteristic analysis showed that all near Dmax parameters were able to predict complication risk, which retained statistical significance after adjusting other variables (odds ratio 1.12 per Gy, 95% confidence interval 1.02-1.23) with positive dose-response relationship. In multiple linear regression model (R 2 = 0.92), conventional fractionation (ß = 11.7) and 16 fractions in 2.66 Gy regimen (ß = 3.9) were the major determinants of near Dmax compared with 15 fractions in 2.66 Gy regimen, followed by utilization of boost RT (ß = 3.2). The effect of bolus and dose inhomogeneity seemed minor (P > 0.05). The location of hot spot was not close to the high density metal area of the expander, but close to the surrounding areas of partially deflated expander bag. Conclusions: This study is the first to demonstrate a dose-response relationship between risk of complications and near Dmax, where hypofractionated regimen or boost RT can play an important role. Rigorous RT-quality assurance program and modification of dose constraints could be considered as a critically important component for ongoing trials of hypofractionation. Based on our findings, we initiated a multi-center retrospective study (KROG 18-04) and a prospective study (NCT03523078) to validate our findings.

The Effect of Hospital Case Volume on Clinical Outcomes in Patients with Nasopharyngeal Carcinoma: A Multi-institutional Retrospective Analysis (KROG-1106).

PURPOSE: The purpose of this study was to investigate the effect of hospital case volume on clinical outcomes in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Data on 1,073 patients with cT1-4N0-3M0 NPC were collected from a multi-institutional retrospective database (KROG 11-06). All patients received definitive radiotherapy (RT) either with three-dimensional-conformal RT (3D-CRT) (n=576) or intensity-modulated RT (IMRT) (n=497). The patients were divided into two groups treated at high volume institution (HVI) (n=750) and low volume institution (LVI) (n=323), defined as patient volume ≥ 10 (median, 13; range, 10 to 18) and < 10 patients per year (median, 3; range, 2 to 6), respectively. Endpoints were overall survival (OS) and loco-regional progression-free survival (LRPFS). RESULTS: At a median follow-up of 56.7 months, the outcomes were significantly better in those treated at HVI than at LVI. For the 614 patients of propensity score-matched cohort, 5-year OS and LRPFS were consistently higher in the HVI group than in the LVI group (OS: 78.4% vs. 62.7%, p < 0.001; LRPFS: 86.2% vs. 65.8%, p < 0.001, respectively). According to RT modality, significant difference in 5-year OS was observed in patients receiving 3D-CRT (78.7% for HVI vs. 58.9% for LVI, p < 0.001) and not in those receiving IMRT (77.3% for HVI vs. 75.5% for LVI, p=0.170). CONCLUSION: A significant relationship was observed between HVI and LVI for the clinical outcomes of patients with NPC. However, the difference in outcome becomes insignificant in the IMRT era, probably due to the standardization of practice by education.

Patterns of failures after surgical resection in olfactory neuroblastoma.

INTRODUCTION: Patterns of failure in patients with olfactory neuroblastoma (ONB) according to two surgical approaches, craniofacial resection (CFR) and endoscopic surgery (ENDO), have yet to be analyzed. METHODS: We retrospectively reviewed 28 patients with surgically treated ONB between January 1995 and October 2017. Fourteen (50.0%) patients underwent CFR (9 CFR alone, 5 ENDO-assisted CFR) and 14 (50.0%) underwent ENDO. Nineteen (67.9%) patients underwent post-operative radiotherapy (RT). RESULTS: At a median follow-up of 53.8 months (range 10.4-195.3), the 5-year progression-free survival (PFS) and 10-year overall survival were 37.3% and 57.5%, respectively. Patients with adjuvant RT had a 5-year PFS of 46.7%, whereas those treated with surgery alone had a 5-year PFS of 19.4% (p = 0.01). Locoregional failure (LRF) occurred in ten patients (median 59.6 months after initial diagnosis; range 12.7-59.7). Neck node metastasis occurred in 25.0% (7 of 28). Five patients with ENDO showed LRF and underwent proper subsequent treatments with either surgery or adjuvant RT. Approximately 35.7% patients (five patients) in the CFR group experienced distant metastasis in the intracranial dura region (median 116.4 months after initial diagnosis; range 2.6-142.4). Three of four patients who developed LRF after CFR developed dura-based metastasis. CONCLUSIONS: Both dura-based and neck node metastasis in the delayed phase were distinct patterns of failure in ONB. Patterns of recurrence differed based on surgical approach; dura-based metastases were common after CFR. LRF was the distinct failure pattern in ENDO, but could be successfully salvaged. Treatment outcome was improved considerably with RT following surgical resection.

The Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Head and Neck Cancer Patients Treated with Radiotherapy.

BACKGROUND: To investigate the prognostic value of pre-treatment neutrophil/lymphocyte ratio (NLR) in patients treated with definitive radiotherapy (RT) for head and neck cancer. METHODS: We retrospectively analyzed 621 patients who received definitive RT for nasopharyngeal, oropharyngeal, hypopharyngeal, and laryngeal cancer. An NLR cut-off value of 2.7 was identified using a receiver operating characteristic curve analysis, with overall survival (OS) as an endpoint. RESULTS: The 5-year progression-free survival (PFS) and OS for all patients were 62.3% and 72.1%, respectively. The patients with a high NLR (68%) had a significantly lower 5-year PFS and OS than their counterparts with a low NLR (32%) (PFS: 39.2% vs. 75.8%, p < 0.001; OS: 50.9% vs. 83.8%, p < 0.001). In a subgroup analysis according to primary site, a high NLR also correlated with a lower PFS and OS, except in oropharyngeal cancer, where a high NLR only exhibited a trend towards lower survival. In a multivariate analysis, a high NLR remained an independent prognostic factor for PFS and OS. CONCLUSION: Head and neck cancer tends to be more aggressive in patients with a high NLR, leading to a poorer outcome after RT. The optimal therapeutic approaches for these patients should be reevaluated, given the unfavorable prognosis.

Prognostic Significance of Sarcopenia With Inflammation in Patients With Head and Neck Cancer Who Underwent Definitive Chemoradiotherapy.

Purpose: With growing evidence that inflammation and low muscularity play a role in the survival of cancer patients, we evaluated the prognostic implications of sarcopenia with systemic inflammation in patients who underwent definitive chemoradiotherapy (CCRT) for locally advanced head and neck cancer. Materials and Methods: We analyzed 221 patients with head and neck cancer who received definitive CCRT between 2006 and 2015. The skeletal muscle area was measured using a single computed tomography image slice at the level of the third lumbar vertebra (L3). Sarcopenia was defined as an L3 muscle index of <49 cm2/m2 for men and <31 cm2/m2 for women. Results: Patients with sarcopenia (n = 106) exhibited higher neutrophil/lymphocyte ratios (NLRs) than those without (n = 115); the former also had an inferior 3-year overall survival (OS) rate (62%) than the latter (76%, p = 0.037). Among patients with sarcopenia, those who also had high NLRs (n = 51) showed significantly poorer OS and progression-free survival (PFS). In the multivariate analysis, sarcopenia plus a high NLR remained the most significant predictor of poor OS and PFS. Patients with sarcopenia required more frequent interruption of RT; patients whose RT was interrupted for ≥5 days showed inferior disease control and OS. Conclusions: Sarcopenia accompanied by systemic inflammation at initial diagnosis is associated with significantly inferior OS and PFS. Additionally, patients with sarcopenia required RT interruption more frequently. Intensive nutritional support and additional treatment methods are required for these patients while undergoing RT.