Assessment and validation of glottic motion using cone-beam CT and real-time cine MRI.

PURPOSE: This study aimed to assess the margin for the planning target volume (PTV) using the Van Herk formula. We then validated the proposed margin by real-time magnetic resonance imaging (MRI). METHODS: An analysis of cone-beam computed tomography (CBCT) data from early glottic cancer patients was performed to evaluate organ motion. Deformed clinical target volumes (CTV) after rigid registration were acquired using the Velocity program (Varian Medical Systems, Palo Alto, CA, USA). Systematic (Σ) and random errors (σ) were evaluated. The margin for the PTV was defined as 2.5 Σ + 0.7 σ according to the Van Herk formula. To validate this margin, we accrued healthy volunteers. Sagittal real-time cine MRI was conducted using the ViewRay system (ViewRay Inc., Oakwood Village, OH, USA). Within the obtained sagittal images, the vocal cord was delineated. The movement of the vocal cord was summed up and considered as the internal target volume (ITV). We then assessed the degree of overlap between the ITV and the PTV (vocal cord plus margins) by calculating the volume overlap ratio, represented as (ITV∩PTV)/ITV. RESULTS: CBCTs of 17 early glottic patients were analyzed. Σ and σ were 0.55 and 0.57 for left-right (LR), 0.70 and 0.60 for anterior-posterior (AP), and 1.84 and 1.04 for superior-inferior (SI), respectively. The calculated margin was 1.8 mm (LR), 2.2 mm (AP), and 5.3 mm (SI). Four healthy volunteers participated for validation. A margin of 3 mm (AP) and 5 mm (SI) was applied to the vocal cord as the PTV. The average volume overlap ratio between ITV and PTV was 0.92 (range 0.85-0.99) without swallowing and 0.77 (range 0.70-0.88) with swallowing. CONCLUSION: By evaluating organ motion by using CBCT, the margin was 1.8 (LR), 2.2 (AP), and 5.3 mm (SI). The margin acquired using CBCT fitted well in real-time cine MRI. Given that swallowing during radiotherapy can result in a substantial displacement, it is crucial to consider strategies aimed at minimizing swallowing and related motion.

Whole-Genome Sequencing Reveals Mutational Signatures Related to Radiation-Induced Sarcomas and DNA-Damage-Repair Pathways.

Radiation-induced sarcoma (RIS) is a rare but serious late complication arising from radiotherapy. Despite unfavorable clinical outcomes, the genomic footprints of ionizing radiation in RIS development remain largely unknown. Hence, this study aimed to characterize RIS genomes and the genomic alterations in them. We analyzed whole-genome sequencing in 11 RIS genomes matched with normal genomes to identify somatic alterations potentially associated with RIS development. Furthermore, the abundance of mutations, mutation signatures, and structural variants in RIS were compared with those in radiation-naïve spontaneous sarcomas. The mutation abundance in RIS genomes, including one hypermutated genome, was variable. Cancer-related genes might show different types of genomic alterations. For instance, NF1, NF2, NOTCH1, NOTCH2, PIK3CA, RB1, and TP53 showed singleton somatic mutations; MYC, CDKN2A, RB1, and NF1 showed recurrent copy number alterations; and NF2, ARID1B, and RAD51B showed recurrent structural variations. The genomic footprints of nonhomologous end joining are prevalent at indels of RIS genomes compared with those in spontaneous sarcoma genomes, representing the genomic hallmark of RIS genomes. In addition, frequent chromothripsis was identified along with predisposing germline variants in the DNA-damage-repair pathways in RIS genomes. The characterization of RIS genomes on a whole-genome sequencing scale highlighted that the nonhomologous end joining pathway was associated with tumorigenesis, and it might pave the way for the development of advanced diagnostic and therapeutic strategies for RIS.

Effect of postoperative radiotherapy for patients with differentiated thyroid cancer.

OBJECTIVE: We evaluated the efficacy and safety of postoperative radiotherapy (PORT) for differentiated thyroid cancer (DTC) with high risk features. MATERIALS AND METHODS: This retrospective study analyzed 187 patients treated for DTC from 1985 to 2019. DTC referred to nonanaplastic thyroid cancer originating from follicular cells. PORT was defined as the administration of external beam radiation to the thyroid and regional lymph nodes following surgery for initially diagnosed DTC. The patients were included in the analysis if they received PORT or exhibited any of the following features: (a) pT4 or pN1b according to the 8th American Joint Committee on Cancer, (b) poorly differentiated thyroid cancer (PDTC), or (c) unfavourable variants such as anaplastic foci and etc. After 1:1 propensity matching, a total of 108 patients were analyzed according to PORT receipt. The median follow-up duration of the matched group was 10.4 years. RESULTS: After matching, most of the variables became balanced, but the PORT group still had more PDTC and DTC with anaplastic foci. Radioactive iodine (RAI) was less frequently administered in the PORT group. PORT yielded a significantly higher 5-year locoregional recurrence free survival (LRFS) than the No PORT group (5-year LRFS 86.1% vs. 72.7%, p = 0.022), but the 10-year cancer specific survival (CSS) was similar between them (97.8% vs. 85.9%, p = 0.122). The multivariable analysis indicated that PORT was a favourable prognostic factor (Hazard ratio 0.3, 95% Confidence interval 0.1-0.8, p = 0.02) for LRFS, but not for CSS. Among 133 patients without PORT for initial disease, 39 of them received salvage surgery followed by salvage PORT. No severe toxicity after PORT was reported. CONCLUSION: PORT reduced locoregional recurrence in DTC patients without severe toxicity. PORT can be an effective and safe treatment to improve locoregional control in DTC with high risk features. However, further study is warranted to identify those who can benefit from PORT.

Development of an anthropomorphic multimodality pelvic phantom for quantitative evaluation of a deep-learning-based synthetic computed tomography generation technique.

PURPOSE: The objective of this study was to fabricate an anthropomorphic multimodality pelvic phantom to evaluate a deep-learning-based synthetic computed tomography (CT) algorithm for magnetic resonance (MR)-only radiotherapy. METHODS: Polyurethane-based and silicone-based materials with various silicone oil concentrations were scanned using 0.35 T MR and CT scanner to determine the tissue surrogate. Five tissue surrogates were determined by comparing the organ intensity with patient CT and MR images. Patient-specific organ modeling for three-dimensional printing was performed by manually delineating the structures of interest. The phantom was finally fabricated by casting materials for each structure. For the quantitative evaluation, the mean and standard deviations were measured within the regions of interest on the MR, simulation CT (CTsim ), and synthetic CT (CTsyn ) images. Intensity-modulated radiation therapy plans were generated to assess the impact of different electron density assignments on plan quality using CTsim and CTsyn . The dose calculation accuracy was investigated in terms of gamma analysis and dose-volume histogram parameters. RESULTS: For the prostate site, the mean MR intensities for the patient and phantom were 78.1 ± 13.8 and 86.5 ± 19.3, respectively. The mean intensity of the synthetic image was 30.9 Hounsfield unit (HU), which was comparable to that of the real CT phantom image. The original and synthetic CT intensities of the fat tissue in the phantom were -105.8 ± 4.9 HU and -107.8 ± 7.8 HU, respectively. For the target volume, the difference in D95% was 0.32 Gy using CTsyn with respect to CTsim values. The V65Gy values for the bladder in the plans using CTsim and CTsyn were 0.31% and 0.15%, respectively. CONCLUSION: This work demonstrated that the anthropomorphic phantom was physiologically and geometrically similar to the patient organs and was employed to quantitatively evaluate the deep-learning-based synthetic CT algorithm.

Correlation between 3D scanner image and MRI for tracking volume changes in head and neck cancer patients.

INTRODUCTION: We investigated the correlation between optical surface imaging using a three-dimensional (3D) scanner and magnetic resonance imaging (MRI) for suggesting feasibility in the clinical process of tracking volume changes in head and neck patients during radiation treatment. METHODS: Ten patients were divided into two groups depending on the location of their tumor (i.e., right or left side). With weekly imaging data, the change in volume based on MRI was evaluated during the treatment course. Four volumes of interest (VOIs) were calculated on the 3D surface image of the facial and cervical areas using an optical 3D scanner, and the correlation between volumetric parameters were analyzed. RESULTS: The target volume changed significantly overall for both groups. The changes parotid volume reduced by up to 3.8% and 28.0% for groups A (right side) and B (left side), respectively. In Group A, VOI 1 on the facial area and VOI 3 on the cervical area decreased gradually during the treatment course by up to 3.3% and 10.7%, respectively. In Group B, only VOI 4 decreased gradually during the treatment course and reduced by up to 9.2%. In group A, the change in target volume correlated strongly with right-side parotid, VOI 1, and VOI 3, respectively. The parotid also showed strong correlations with VOIs (P < 0.01). The weight loss was strongly correlated with either PTV or parotid without statistical significance (P > 0.05). In group B (left side), the change in target volume correlated strongly with each volumetric parameter, including weight loss. For individual patient, PTV showed more correlation with VOIs on the cervical area than VOIs on the facial area. CONCLUSIONS: An optical 3D scanner can be applied to track changes in volume without radiation exposure during treatment and the optical surface image correlated with MRI.

Severe late dysphagia after multimodal treatment of stage III/IV laryngeal and hypopharyngeal cancer.

BACKGROUND: Long-term side effects after radiotherapy for organ preservation 'could deteriorate' the laryngeal function. This study intended to identify the incidence of severe late dysphagia following the multimodal treatment for stage III/IV laryngeal and hypopharyngeal cancer 'to evaluate the function of larynx'. METHODS: The medical records of patients successfully treated for laryngeal and hypopharyngeal cancer with a multimodal approach, including radiotherapy, were retrospectively analyzed. 'Functional larynx was defined as tolerable oral diet without severe late dysphagia or tracheostoma'. RESULTS: The study included 99 patients with a median follow-up period of 72 months. 'Tracheostomy during the follow-up period was required in only one patient due to aspiration pneumonia, and dysphagia is the main determinant for functional larynx'. The probability of maintaining functional larynx was 63% for 10 years, when the treatment was started with radiotherapy or concurrent chemoradiotherapy. In upfront surgery (operation first and adjuvant radiotherapy/concurrent chemoradiotherapy) group, 37% of patients required total laryngectomy as primary treatment and 43% of patients could maintain laryngeal function for 10 years. And severe late dysphagia in the latter group developed mainly after laryngeal preservation surgery. The patients aged ≥65 years showed significantly higher incidence of dysphagia. Severe late dysphagia was very rare in laryngeal cancer successfully cured with radiotherapy/concurrent chemoradiotherapy (1/25, 4%); however, it gradually increased over time in hypopharyngeal cancer patients showing a statistically significant difference from laryngeal cancer patients (P = 0.040). CONCLUSION: Severe late dysphagia occurred in 19.2% of patients treated for laryngeal and hypopharyngeal cancers, regardless of whether treatment started with radiotherapy/concurrent chemoradiotherapy or surgery.

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

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

Air-electron stream interactions during magnetic resonance IGRT : Skin irradiation outside the treatment field during accelerated partial breast irradiation.

PURPOSE: To investigate and to prevent irradiation outside the treatment field caused by an electron stream in the air generated by the magnetic field during magnetic resonance image-guided accelerated partial breast irradiation (APBI). MATERIALS AND METHODS: In all, 20 patients who received APBI with a magnetic resonance image-guided radiation therapy (MR-IGRT) system were prospectively studied. The prescription dose was 38.5 Gy in 10 fractions of 3.85 Gy and delivered with a tri-cobalt system (the ViewRay system). For each patient, primary plans were delivered for the first five fractions and modified plans with different gantry angles from those of the primary plan (in-treatment plans) were delivered for the remaining five fractions to reduce the skin dose. A 1 cm thick bolus was placed in front of the patient's jaw, ipsilateral shoulder, and arm to shield them from the electron stream. Radiochromic EBT3 films were attached to the front (towards the breast) and back (towards the head) of the bolus during treatment. Correlations between the measured values and the tumor locations, treatment times, and tumor sizes were investigated. RESULTS: For a single fraction delivery, the average areas of the measured isodoses of 14% (0.54 Gy), 12% (0.46 Gy), and 10% (0.39 Gy) at the front of the boluses were as large as 3, 10.4, and 21.4 cm2, respectively, whereas no significant dose could be measured at the back of the boluses. Statistically significant but weak correlations were observed between the measured values and the treatment times. CONCLUSION: During radiotherapy for breast cancer with an MR-IGRT system, the patient must be shielded from electron streams in the air generated by the interaction of the magnetic field with the beams of the three-cobalt treatment unit to avoid unwanted irradiation of the skin outside the treatment field.

Intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy in rectal cancer treated with neoadjuvant concurrent chemoradiation: a meta-analysis and pooled-analysis of acute toxicity.

BACKGROUND: To compare the acute gastrointestinal (GI) and genitourinary (GU) toxicity profiles between intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in rectal cancer patients treated with neoadjuvant chemoradiation (NCRT) using meta-analysis and pooled-analysis from published articles. METHODS: Literature search was performed in PubMed and EMBASE from inception to March 2017. The odd ratios (ORs) were calculated and random effects model was used for meta-analysis. Chi-square or Fisher's exact test was performed for the pooled-analysis. RESULTS: Six studies including a total of 859 patients met the inclusion criteria. Most patients (98.7%) received NCRT. In the meta-analysis, IMRT reduced grade ≥ 2 acute overall GI toxicity, diarrhea and proctitis with ORs of 0.38, 0.32 and 0.60, respectively (all P < 0.05), compared to 3DCRT. IMRT also reduced acute grade ≥ 3 proctitis compared to 3D-CRT (OR, 0.24; P = 0.03). No significant heterogeneity or publication bias was detected. In the pooled-analysis, IMRT reduced the incidence of grade ≥ 2 acute overall GI toxicity, diarrhea, proctitis and GU toxicity (all P < 0.05). Moreover, lower incidence of grade ≥ 3 acute overall GI toxicity, diarrhea and proctitis were observed in the patients treated with IMRT (all P < 0.05). CONCLUSIONS: IMRT significantly reduced acute toxicity in locally advanced rectal cancer patients treated with NCRT compared to 3DCRT.

Development and validation of the smart management strategy for health assessment tool-short form (SAT-SF) in cancer survivors.

PURPOSE: The aim of this study was to develop and validate a short form (SF) of the Smart Management Strategy for Health Assessment Tool (SAT) for cancer patients. METHODS: Data for item reduction were derived from cancer patient data (n = 300) previously used to develop the original SAT. We used regression methods to select and score the new SAT-SF. To assess the instrument's reliability and validity, we recruited another 354 cancer patients from the same hospitals who were older than 18 years and accustomed to using the web. All results were compared with that of the long-form SAT (original SAT). RESULTS: The SAT-SF used is the shorter version, a 30-item (from the original 91-item) instrument, to measure cancer patient's health. The 30-item SAT-SF explained 97.7% of total variance of the full 91-item long-form SAT. All SAT-SF subscales demonstrated a high reliability with good internal consistency compared with the original SAT. The total short-form scores of the three SAT sets (SAT-Core, SAT-Preparation, SAT-Implementation) differentiated participant groups according to their stage of goal implementation and percentage of actions taken in the 10 Rules for Highly Effective Health Behavior. We found acceptable correlations between the three SAT-SF sets and the additional assessment tools compared with the original SAT. CONCLUSIONS: The 30-item SAT-SF had a satisfactory internal consistency and validity for cancer patients with minimal loss of information compared with the original SAT.

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.

Perceived needs for the information communication technology (ICT)-based personalized health management program, and its association with information provision, health-related quality of life (HRQOL), and decisional conflict in cancer patients.

OBJECTIVE: The use of information communication technology (ICT)-based tailored health management program can have significant health impacts for cancer patients. Information provision, health-related quality of life (HRQOL), and decision conflicts were analyzed for their relationship with need for an ICT-based personalized health management program in Korean cancer survivors. METHODS: The health program needs of 625 cancer survivors from two Korean hospitals were analyzed in this cross-sectional study. Multivariate logistic regression was used to identify factors related to the need for an ICT-based tailored health management system. Association of the highest such need with medical information experience, HRQOL, and decision conflicts was determined. Furthermore, patient intentions and expectations for a web- or smartphone-based tailored health management program were investigated. RESULTS: Cancer survivors indicated high personalized health management program needs. Patients reporting the highest need included those with higher income (adjusted odds ratio [aOR], 1.70; 95% [confidence interval] CI, 1.10-2.63), those who had received enough information regarding helping themselves (aOR, 1.71; 95% CI, 1.09-2.66), and those who wished to receive more information (aOR, 1.59; 95% CI, 0.97-2.61). Participants with cognitive functioning problems (aOR, 2.87; 95%CI, 1.34-6.17) or appetite loss (aOR, 1.77; 95% CI, 1.07-2.93) indicated need for a tailored health care program. Patients who perceived greater support from the decision-making process also showed the highest need for an ICT-based program (aOR, 0.49; 95% CI, 0.30-0.82). CONCLUSIONS: We found that higher income, information provision experience, problematic HRQOL, and decisional conflicts are significantly associated with the need for an ICT-based tailored self-management program.

Clinical outcomes of stereotactic ablative radiotherapy in patients with pulmonary metastasis.

BACKGROUNDS: In addition to its curative use for early stage lung cancer, stereotactic ablative radiotherapy is also indicated for pulmonary metastatic disease. Aims of this study were to retrospectively analyze treatment outcomes and to find prognostic factors for survivals. METHODS: Treatment outcomes and toxicities of 85 cases of SABR in 72 patients were retrospectively reviewed from September 2012 to April 2015. Prognostic factors were analyzed using Cox proportional hazards regression. RESULTS: The local failure-free survival rate at 2 years was 98%. Of the case, 1-year and 2-year progression-free survival rates were 62% and 48%, and overall survival rates were 90% and 72%, respectively. Multivariate analyses demonstrated that controlled primary cancer (P = 0.01), absence of extra-pulmonary metastatic disease (P < 0.01) and disease-free interval longer than 1 year (P < 0.01) favorably affected progression-free survival. Furthermore, the absence of extra-pulmonary metastatic disease (P < 0.01) increased overall survival as well. Grade 1 or 2 radiation pneumonitis was found in 37 cases, and Grade 1 chest wall pain was found in 1 case. CONCLUSIONS: Stereotactic ablative radiotherapy demonstrated good local control with tolerable adverse effects for pulmonary metastasis. The presence or absence of extra-pulmonary metastasis was found to be prognostic factor of mortality after stereotactic ablative radiotherapy treatment.

Implication of Tumor Location for Lymph Node Metastasis in Maxillary Sinus Carcinoma: Indications for Elective Neck Treatment.

PURPOSE: For either neck irradiation or dissection, the indications for elective neck treatment (ENT) of maxillary sinus carcinoma are still unclear. The purpose of the present study was to investigate the relationship between the anatomic extent of the disease and lymph node metastasis in maxillary sinus carcinoma and to propose a recommendation regarding ENT. MATERIALS AND METHODS: In the present retrospective cohort study, patients with squamous cell carcinoma (SCC) and undifferentiated carcinoma (UDC) of maxillary sinus treated with radical intent from January 1995 to June 2015 in a single institution were recruited by retrospective medical record review. The demographic and tumor characteristics of the patients and maxillary sinus wall invasion, verified on pretreatment volumetric imaging studies, were analyzed. The Cox proportional hazards model was used to find the risk factors for nodal relapse, distant metastasis, and survival. RESULTS: Among a total of 71 identified patients, 66 had SCC and 5 had UDC. In 55 patients with node-negative disease, the risk of ipsilateral nodal relapse was 25.1% without ENT. In contrast, no ipsilateral nodal relapse was reported after ENT. On multivariate analysis, no chemotherapy (hazard ratio [HR] = 7.25; P = .01), posterior wall invasion (HR = 6.51; P = .03), and local failure (HR = 6.42; P = .02) were identified to be the risk factors of nodal relapse. Nodal relapse influenced the risk of distant metastasis with marginal significance (HR = 3.95; P = .07) but did not have an effect on survival. The most common regions of lymph node metastasis, at both initial presentation and relapse, were ipsilateral levels I and II. CONCLUSIONS: For SCC and UDC of the maxillary sinus with posterior wall invasion, ENT involving ipsilateral levels I and II is recommended. Future studies with larger numbers of patients are needed to validate our conclusion.

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).

Predictive and prognostic value of PET/CT imaging post-chemoradiotherapy and clinical decision-making consequences in locally advanced head & neck squamous cell carcinoma: a retrospective study.

BACKGROUND: The accuracy of (18)F-fluorodeoxygluocose positron emission tomography/computed tomography (PET/CT) in predicting immediate failure after radical chemoradiotherapy (CRT) for HNSCC is poorly characterized at present. The purpose of this study was to examine PET/CT as a predictive and prognostic gauge of immediate failure after CRT and determine the impact of these studies on clinical decision making in terms of salvage surgery. METHODS: Medical records of 78 consecutive patients receiving radical CRT for locally advanced HNSCC were reviewed, analyzing PET/CTs done before and 3 months after CRT. Immediate failure was defined as residual disease or locoregional and/or systemic relapse within 6 months after CRT. RESULTS: Maximum standard uptake value (SUV) of post CRT PET/CT (postSUVmax) was found optimal for predicting immediate failure at a cutpoint of 4.4. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were 90.0%, 83.8%, 98.3%, and 45.0%, respectively. Of 78 patients studied, postSUVmax ≥ 4.4 prevailed in 20 (25.6%), with postSUVmax <4.4 in 58 (74.4%). At postSUVmax ≥ 4.4 (vs. postSUVmax <4.4) OS was poorer by comparison (3-year OS: 56.9 vs. 87.7%; P = 0.005), as was progression-free survival (3-year PFS: 42.9 vs. 81.1%; P < 0.001). At postSUVmax ≥ 4.4, OS with and without immediate salvage surgery did not differ significantly (3-year OS: 60.0 vs. 55.6%; Log-rank P = 0.913). CONCLUSION: Post CRT PET/CT imaging has prognostic value in terms of OS and PFS and is useful in predicting immediate therapeutic failure, given its high NPV. However, OS was not significantly altered by early salvage surgery done on the basis of post CRT PET/CT findings.

A Randomized, Multicenter, Phase II Study of Cetuximab With Docetaxel and Cisplatin as Induction Chemotherapy in Unresectable, Locally Advanced Head and Neck Cancer.

BACKGROUND: We investigated the efficacy of cetuximab when added to induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in patients with locally advanced head and neck squamous cell carcinoma. METHODS: Patients were randomized to receive three cycles of docetaxel and cisplatin (TP regimen) with or without cetuximab (TP plus cetuximab [CTP] vs. TP) as induction chemotherapy. Patients in the CTP arm received CCRT with cetuximab and cisplatin, whereas patients in the TP arm received cisplatin alone. The primary endpoint was the objective response rate (ORR) after induction chemotherapy. RESULTS: Overall, 92 patients were enrolled. The ORRs for induction chemotherapy in the CTP and TP arms were not different (81% vs. 82%). Adding cetuximab lowered the completion rate of induction chemotherapy and CCRT and resulted in more frequent dose reductions of the induction chemotherapy, although this did not reach statistical significance. In the CTP and TP arms, respectively, the 3-year progression-free survival (PFS) rates were 70% and 56% (p = .359), and the overall survival (OS) rates were 88% and 74% (p = .313). When limited to patients who completed induction chemotherapy, 3-year PFS rates of 78% and 59% (p = .085) and OS rates of 94% and 73% (p = .045) were observed in the CTP and TP arms, respectively. CONCLUSION: Adding cetuximab to sequential treatment did not increase the treatment efficacy and resulted in greater toxicity. In the intent-to-treat population, neither PFS nor OS was improved by the addition of cetuximab to sequential treatment; however, a suggestion of improved survival outcomes was observed in patients completing cetuximab-containing induction chemotherapy.

Radiosensitization with combined use of olaparib and PI-103 in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) shows aggressive clinical behavior, but the treatment options are limited due to lack of a specific target. TNBC shares many clinical and pathological similarities with BRCA-deficient breast cancer, for which poly(ADP-ribose) polymerase (PARP) inhibitor is effective, but PARP inhibitor alone failed to show clinical effects in patients with sporadic TNBC. Radiation induces DNA double-strand breaks, and the phosphoinositide 3-kinase (PI3K) signaling pathway has been known to regulate steady-state levels of homologous recombination. A recent preclinical study showed that PI3K inhibition impairs BRCA1/2 expression and sensitizes BRCA-proficient TNBC to PARP inhibition. Therefore, we assessed the radiosensitizing effect, and the underlying mechanism of combination treatment with PARP inhibitor olaparib and PI3K inhibitor PI-103 in BRCA-proficient TNBC cells. METHODS: MDA-MB-435S cells were divided into four treatment groups, irradiation (IR) alone, olaparib plus IR, PI-103 plus IR, and olaparib plus PI-103 plus IR. Cells were exposed to the drugs for 2 hours prior to irradiation, and the cell survival curve was obtained using a clonogenic assay. Western blotting and immunofluorescent detection of γH2AX foci were performed. Xenograft and bioluminescence imaging were carried out to assess in vivo radiosensitivity. RESULTS: Combined use of olaparib and PI-103 enhanced radiation-induced death of MDA-MB-435S (sensitizer enhancement ratio[SER]0.05,1.7) and MDA-MB-231-BR (SER0.05,2.1) cells and significantly reduced tumor volume in a xenograft models (P < 0.001). Treatment with PI-103 showed persistent γH2AX foci, indicating delayed repair of DNA strand breaks. PI-103 alone increased levels of poly(ADP-ribose) and phosphorylated extracellular signal-regulated kinase, and downregulated BRCA1. CONCLUSIONS: Combined use of olaparib and PI-103 enhanced radiation-induced cell death in BRCA-proficient MDA-MB-435S and MDA-MB-231-BR cells and xenografts. TNBC patients have high incidences of locoregional relapse and distant metastasis, and radiation therapy targets both locoregional control and treatment of distant recurrences such as brain metastasis or other oligometastasis. Targeting of the PI3K signaling pathway combined with PARP inhibition maybe a feasible approach to enhance effects of radiation in BRCA-proficient TNBC.

Patient-reported assessment of self-management strategies of health in cancer patients: development and validation of the Smart Management Strategy for Health Assessment Tool (SAT).

OBJECTIVE: The objective of this study was to evaluate the psychometric properties of the Smart Management Strategy for Health Assessment Tool (SAT), which we developed to enable cancer patients to assess their self-management (SM) strategies of health by themselves. PATIENTS AND METHODS: The development of the questionnaire included four phases: item generation, construction, pilot testing, and field testing. To assess the instrument's sensitivity and validity, we recruited 300 cancer patients from three Korean hospitals who were 18 or more years old and accustomed to using the Internet or email. Using the appropriate and priority criteria for pilot and field testing, we tightened the content and constructed the first version of the SAT. RESULTS: We developed the core strategies with 28 items, preparation strategies with 30 items, and implementation strategies with 33 items. Factor analysis of data from 300 patients resulted in core strategies with four factors, preparation strategies with five factors, and implementation strategies with six factors. All the SAT subscales demonstrated a high reliability with good internal consistency. The total scores of the three SAT sets differentiated participant groups well according to their stage of goal implementation and proportions of action of the 10 Rules for Highly Effective Health Behavior. Each factor of the three SAT sets correlated positively with the scores for additional assessment tool. CONCLUSION: The SAT is a three-set, 16-factor, 91-item tool that assesses the SM strategies of health that patients use to overcome a crisis. Patients can use the SAT to assess their SM strategies of health and obtain feedback from clinicians in the practice setting.