Methodological approach for determining the Minimal Important Difference and Minimal Important Change scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module (EORTC QLQ-HN43) exemplified by the Swallowing scale.

PURPOSE: The aim of this study was to explore what methods should be used to determine the minimal important difference (MID) and minimal important change (MIC) in scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43. METHODS: In an international multi-centre study, patients with head and neck cancer completed the EORTC QLQ-HN43 before the onset of treatment (t1), three months after baseline (t2), and six months after baseline (t3). The methods explored for determining the MID were: (1) group comparisons based on performance status; (2) 0.5 and 0.3 standard deviation and standard error of the mean. The methods examined for the MIC were patients' subjective change ratings and receiver-operating characteristics (ROC) curves, predictive modelling, standard deviation, and standard error of the mean. The EORTC QLQ-HN43 Swallowing scale was used to investigate these methods. RESULTS: From 28 hospitals in 18 countries, 503 patients participated. Correlations with the performance status were |r|< 0.4 in 17 out of 19 scales; hence, performance status was regarded as an unsuitable anchor. The ROC approach yielded an implausible MIC and was also discarded. The remaining approaches worked well and delivered MID values ranging from 10 to 14; the MIC for deterioration ranged from 8 to 16 and the MIC for improvement from - 3 to - 14. CONCLUSIONS: For determining MIDs of the remaining scales of the EORTC QLQ-HN43, we will omit comparisons of groups based on the Karnofsky Performance Score. Other external anchors are needed instead. Distribution-based methods worked well and will be applied as a starting strategy for analyses. For the calculation of MICs, subjective change ratings, predictive modelling, and standard-deviation based approaches are suitable methods whereas ROC analyses seem to be inappropriate.

Accelerated partial breast irradiation by brachytherapy: present evidence and future developments.

Accelerated partial breast irradiation (APBI) delivers a short course of adjuvant RT after breast conserving surgery to only a limited part of the breast where the tumor was located. This procedure requires expertise, good communication, and close collaboration between specialized surgeons and attending radiation oncologists with adequate intraoperative tumor bed clip marking. However, APBI offers several intrinsic benefits when compared with whole breast irradiation (WBIR) including reduced treatment time (1 versus 4-6 weeks) and better sparing of surrounding healthy tissues. The present publication reviews the APBI level 1-evidence provided with various radiation techniques supplemented by long-term experience obtained from large multi-institutional phase II studies. Additionally, it offers an outlook on recent research with ultra-short or single-fraction APBI courses and new brachytherapy sources. Mature data from three randomized controlled trials (RCTs) clearly prove the noninferiority of APBI with 'only two techniques-1/MIBT (multicatheter interstitial brachytherapy) (two trials) and 2/intensity modulated radiotherapy (one trial)'-in terms of equivalent local control/overall survival to the previous standard 'conventionally fractionated WBIR'. However, MIBT-APBI techniques were superior in both toxicity and patient-reported outcomes (PROs) versus WBIR at long-term follow-up. Currently, in RCT-setting, alternative APBI techniques such as intraoperative electrons, 50-kV x-rays and three-dimensional conformal external beam radiotherapy (3D-CRT) failed to demonstrate noninferiority to conventionally fractionated WBIR. However, 3D-CRT-APBI compared noninferior to hypo-fractionated WBIR in preventing ipsilateral breast tumor recurrence (randomized RAPID-trial) but was associated with a higher rate of late radiation toxicity. Ultimately, MIBT remains the only APBI modality with noninferior survival/superior toxicity/PROs at 10-years and therefore should be prioritized over alternative methods in patients with breast cancer considered at low-risk for local recurrence according to recent international guidelines.

Intermediate-term results of trans-abdominal ultrasound (TAUS)-guided brachytherapy in cervical cancer.

OBJECTIVES: To report the intermediate-term results of trans-abdominal ultrasound (TAUS)-guided brachytherapy in cervical cancer. MATERIALS AND METHODS: Ninety-two patients with cervical cancer (stage IB-IVA, according to FIGO staging), were treated by curative radiotherapy from February 2012 to June 2015. All patients were treated with whole pelvic radiotherapy to 50 Gy in 25 fractions and central shielding after 44 Gy, in combination with TAUS-guided brachytherapy, in order to escalate the total dose (EQD2) to the minimal dose at cervical points (in EQD2 concepts) defined by TAUS, while maintaining low doses to ICRU bladder and rectal points. The treatment results and toxicity profiles were reported. RESULTS: At median follow-up time of 41.2 months (range 8 to 61 months) the pelvic control, disease-free survival, and overall survival rates were 84.8%, 75%, and 88%, respectively. The mean applied doses to cervix, bladder, and rectal points were 83.5, 72.3, and 76.5 Gy, respectively. Eight patients developed grade 2 Gastrointestinal toxicity. CONCLUSION: The 3-year results demonstrated that TAUS-guided brachytherapy is feasible and associated with excellent tumor control/toxicity rates in cervical cancer.

Combined chemoradiation of cisplatin versus carboplatin in cervical carcinoma: a single institution experience from Thailand.

BACKGROUND: To report the results of combined chemoradiation (CCRT) with cisplatin versus carboplatin in locally advanced cervical carcinoma. METHODS: From 2009 to 2013, 255 patients with stage IIB-IVA cervical carcinoma, according to FIGO staging were prospectively assigned to be treated with pelvic radiotherapy followed by brachytherapy given concurrently with cisplatin or carboplatin in the treatment of locally advanced cervical cancer. Treatment outcomes and toxicitiy were evaluated. RESULTS: Two-hundred and thirteen patients could be evaluated. At a median follow-up time of 43 months (6-69 months), the 3-year local control, disease-free survival, metastasis-free survival and overall survival rates were 93, 80.8, 85.0 and 87.3 %, respectively. No statistical difference in terms of local control, disease-free survival, metastasis-free survival and overall survival rates between cisplatin and carboplatin treatments was observed in this study. Eighty-six percents of the patients in the carboplatin group could receive more than 4 cycles, while there were only 72 % in the cisplatin group who completed more than 4 cycles (p = 0. 02). In terms of acute toxicity, cisplatin caused significantly more anemia (p = 0.026), neutropenia (p = 0. 044) and nephrotoxicity (p = 0. 031) than carboplatin. No difference in late toxicity was observed in this study. CONCLUSION: Carboplatin yielded comparable results to cisplatin in concurrent chemo-radiation for locally advanced cervical cancer. In addition, carboplatin was associated with a better compliance rate and was associated with less of anemia, neutropenia and nephrotoxicity.

Deep inspiration breath-hold (DIBH) radiotherapy in left-sided breast cancer: Dosimetrical comparison and clinical feasibility in 20 patients.

BACKGROUND: Adjuvant radiotherapy after breast-conserving surgery (BCS) for breast cancer (BC) is a well-established indication. The risk of ischaemic heart disease after radiotherapy for BC increases linearly with the heart mean dose with no apparent threshold. Radiotherapy to the left breast in deep inspiration breath-hold (DIBH) reduces the dose to the heart. A new linac system with an integrated surface scanner (SS) for DIBH treatments was recently installed in our department. We tested it for potential benefits, safety, patients' acceptance/compliance and associated additional workload. MATERIALS AND METHODS: Twenty consecutive patients following BCS for breast carcinoma of the left side were enrolled in our institutional DIBH protocol. We compared dose to the heart and ipsilateral lung (IL) between plans in DIBH and free breathing (FB) using standard defined parameters: mean dose, maximal dose to a volume of 2 cm(3) (D2 cm (3)), volume receiving ≥ 5 Gy (V5), 10 Gy (V10), 15 Gy (V15) and 20 Gy (V20). Comparison of median calculated dose values was performed using a two-tailed Wilcoxon signed rank test. RESULTS: DIBH was associated with a statistically significant reduction (p < 0.001) in all studied parameters for the heart and the IL. In 16 of 20 patients the heart D2 cm (3) was less than 42 Gy in DIBH. In FB the heart D2 cm (3) was ≥ 42 Gy in 17 of 20 patients. The median daily treatment time was 9 min. CONCLUSION: Radiotherapy of the left breast in DIBH using a SS could easily be incorporated into daily routine and is associated with significant dose reduction to the heart and IL.

Preliminary results of adjuvant image-guided vaginal brachytherapy alone for early stage endometrial carcinoma.

Objective: This retrospective study evaluated the preliminary outcomes of image-guided vaginal brachytherapy (IG-VBT) in the adjuvant treatment of high intermediate risk endometrial cancer. Materials and Methods: Data were collected from 48 patients who underwent adjuvant IG-VBT between 2019 and 2022 at the Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University. The vaginal cuff clinical target volume (CTV-VC) is composed of a 4-mm-thick band around vaginal cylinder at the upper 3 cm of the vaginal cuff. A total dose of 21 Gy in three fractions was delivered to the CTV-VC, and the dose to the bladder and rectum were evaluated. Treatment details, patient characteristics, and outcomes were analyzed. Descriptive statistics were used for analysis, and Kaplan-Meier method was employed for survival analysis. Results: The mean age was 62 years, with mainly endometrioid carcinoma pathology (96 %). All patients were at stage I, with 87.5 % receiving complete surgical staging. Mean total treatment time was 10 days with mean D90 of CTV-VC was 29.7 Gy, and D2cc of bladder, rectum, and sigmoid were 24.6 Gy, 21.0 Gy, and 7.7 Gy, respectively. At a median follow-up of 37 months, 3-year local control, disease-free survival, and overall survival rates were 100 %, 100 %, and 97.9 %. respectively. Two patients (4.2 %) experienced grade 1-2 gastrointestinal toxicity, while no genitourinary toxicity or serious adverse events were observed. Conclusions: The preliminary results of IG-VBT in endometrial cancer demonstrated favorable outcomes in terms of vaginal control and toxicity. Further studies with larger cohorts and longer follow-up durations are warranted.

The Value of PET/CT in Particle Therapy Planning of Various Tumors with SSTR2 Receptor Expression: Comparative Interobserver Study.

The overexpression of somatostatin receptor type 2 (SSTR2) is a property of various tumor types. Hybrid imaging utilizing [68Ga]1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra-acetic acid (DOTA) may improve the differentiation between tumor and healthy tissue. We conducted an experimental study on 47 anonymized patient cases including 30 meningiomas, 12 PitNET and 5 SBPGL. Four independent observers were instructed to contour the macroscopic tumor volume on planning MRI and then reassess their volumes with the additional information from DOTA-PET/CT. The conformity between observers and reference volumes was assessed. In total, 46 cases (97.9%) were DOTA-avid and included in the final analysis. In eight cases, PET/CT additional tumor volume was identified that was not detected by MRI; these PET/CT findings were potentially critical for the treatment plan in four cases. For meningiomas, the interobserver and observer to reference volume conformity indices were higher with PET/CT. For PitNET, the volumes had higher conformity between observers with MRI. With regard to SBGDL, no significant trend towards conformity with the addition of PET/CT information was observed. DOTA PET/CT supports accurate tumor recognition in meningioma and PitNET and is recommended in SSTR2-expressing tumors planned for treatment with highly conformal radiation.

Intermediate-term results of image-guided brachytherapy and high-technology external beam radiotherapy in cervical cancer: Chiang Mai University experience.

OBJECTIVE: To evaluate the outcomes of image-guided brachytherapy combined with 3D conformal or intensity modulated external beam radiotherapy (3D CRT/IMRT) in cervical cancer at Chiang Mai University. METHODS: From 2008 to 2011, forty-seven patients with locally advanced cervical cancer were enrolled in this study. All patients received high-technology (3D CRT/IMRT) whole pelvic radiotherapy with a total dose of 45-46 Gy plus image-guided High-Dose-Rate intracavitary brachytherapy 6.5-7 Gy × 4 fractions to a High-Risk Clinical Target Volume (HR-CTV) according to GEC-ESTRO recommendations. The dose parameters of the HR-CTV for bladder, rectum and sigmoid colon were recorded, as well as toxicity profiles. In addition, the endpoints for local control, disease-free, metastasis-free survival and overall survival were calculated. RESULTS: At the median follow-up time of 26 months, the local control, disease-free survival, and overall survival rates were 97.9%, 85.1%, and 93.6%, respectively. The mean dose of HR-CTV, bladder, rectum and sigmoid were 93.1, 88.2, 69.6, and 72 Gy, respectively. In terms of late toxicity, the incidence of grade 3-4 bladder and rectum morbidity was 2.1% and 2.1%, respectively. CONCLUSIONS: A combination of image-guided brachytherapy and IMRT/3D CRT showed very promising results of local control, disease-free survival, metastasis-free survival and overall survival rates. It also caused a low incidence of grade 3-4 toxicity in treated study patients.

Performance of the EORTC questionnaire for the assessment of quality of life in head and neck cancer patients EORTC QLQ-H&N35: a methodological review.

PURPOSE: The EORTC QLQ-H&N35 (H&N35) is widely used to measure quality of life in head and neck cancer patients. The aims of this study were to obtain insight into a) the languages in which the H&N35 has been used and the psychometric properties in those languages, b) the study designs, and c) its acceptance by patients and investigators. METHODS: A systematic literature review was performed searching for all original papers that had used at least one item of the H&N35. Identified papers were read and the information about methodological issues abstracted statistically analysed. RESULTS: A total of 136 papers were identified. The H&N35 was administered in 19 different languages in 27 countries. The study design was cross-sectional in the majority of studies (53 %), prospective cohort studies (31 %), phase-II-trials (7 %), phase-III-trials (6 %) and case-control studies (1 %). The scales with the highest percentages of missing values were Sexuality (11.5 %) and Speech (7 %). The median Cronbach's alpha of the multi-item scales ranged from 0.61 (Senses) to 0.93 (Sexuality). Construct validity was rarely investigated. On average, 12 scales (range 0-18) of the instrument were used by the investigators. The scale most often used was swallowing (in 85 % of studies) and least often used was Weight Gain (39 %). CONCLUSION: The H&N35 is widely used throughout the world, mainly in observational studies, and has demonstrated robust psychometric features in different languages. However, some methodological problems reported imply that the instrument can be improved in some areas.

The association of vagina equivalent dose in 2Gy fraction (EQD2) to late vagina toxicity in patients of cervical cancer treated with WPRT plus IGABT.

AIM: To evaluate the associations of vaginal dose parameters and incidence of vaginal stenosis in patients with cervical cancer treated with image-guided brachytherapy (IGBT). MATERIALS AND METHODS: Fifty-four patients with cervical cancer treated with IGBT were included. The vagina contouring was done on previously treated CT images and the vaginal dose points were marked. The cumulative dose in EQD2 from EBRT and IGBT was calculated for both aspects and the vaginal toxicity was evaluated. RESULTS: At median follow-up time of 18.5 months, grade 2 or higher vaginal stenosis was observed in 24% of patients. On univariate analysis, parameters that were associated with ≥ grade 2 vaginal stenosis were age, mean dose of lateral 5 mm vagina, dose at PIBS-2 cm, mid vaginal D0 .03cc, mid vagina D1cc, lower vagina D0.03cc, lower vagina D0.1cc, lower vagina D1cc and lower vagina D2cc. On multivariate analysis, the significant parameters were age > 68.5 years old (P = 0.038), mean dose of lateral 5-mm (P = 0.034), and dose at PIBS-2 cm (P = 0.042). CONCLUSIONS: Age > 68.5 years old, mean dose of lateral 5 mm vagina and dose at PIBS-2 cm were associated with grade 2 or higher vaginal stenosis.

Brachytherapy dose changes: comparing in-room and out-room image-guided brachytherapy. A randomized study.

Purpose: Image-based brachytherapy, involving an image machine and a brachytherapy unit in the same room (in-room brachytherapy [IRBT]), limits patient movements; however, this technique may not be feasible in high workload centers. In this study, we compared changes in the dose and volume of organs at risk (OARs) with out-room brachytherapy (ORBT) technique, in which patients musted be transferred to a waiting room and then transferred back for brachytherapy delivery. Material and methods: This was a randomized prospective study comparing changes in D2cc doses and volume of OARs during IRBT and ORBT. Patients underwent CT for treatment planning (CT1) installed in brachytherapy loading room, and another CT immediately before brachytherapy (CT2) during each fraction. While patients remained on CT table after CT1 during treatment planning and delivery in IRBT arm, they were transferred out to waiting room and back to CT table in ORBT arm. CT2 was analyzed with CT1 to evaluate any changes in volumes and doses. Results: A total of 294 fractions of brachytherapy were considered. The findings indicated no significant differences in the mean D2cc changes (Gy) (CT2 minus CT1) to the bladder, rectum, and sigmoid between IRBT and ORBT (mean ±SD: -0.07 ±0.36 vs. -0.01 ±0.39, p = 0.1426; -0.15 ±0.32 vs. -0.14 ±0.29, p = 0.8898; -0.17 ±0.38 vs. -0.19 ±0.31, p = 0.5221, respectively). Moreover, significant correlations were observed between D2cc changes and volume changes to each of OARs, p < 0.001. Conclusions: IRBT does not result in differences in dose changes between planning and pre-treatment imaging when compared with ORBT. Consequently, ORBT can be considered for routine practice in high workload centers. Correlations in volume change and dose change to OARs were also observed.

Normofractionated and moderately hypofractionated proton therapy: comparison of acute toxicity and early quality of life outcomes.

Aim: Data on the safety of moderately hypofractionated proton beam therapy (PBT) are limited. The aim of this study is to compare the acute toxicity and early quality of life (QoL) outcomes of normofractionated (nPBT) and hypofractionated PBT (hPBT). Material and methods: We prospectively compared acute toxicity and QoL between patients treated with nPBT (dose per fraction 1.8-2.3 Gy, n = 90) and hPBT (dose per fraction 2.5-3.1 Gy, n = 49) in following locations: head and neck (H&N, n = 85), abdomen and pelvis (A&P, n = 43), and other soft tissue (ST, n = 11). The toxicities were grouped into categories-mucosal, skin, and other sites-and evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 at baseline, treatment completion, and 3 months after PBT completion. QoL was evaluated with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 scale for all locations and additionally with EORTC QLQ-HN35 for H&N patients. Results: Overall, the highest toxicity grades of G0, G1, G2, and G3 were observed in 7 (5%), 40 (28.8%), 78 (56.1%), and 15 (10.8%) patients, respectively. According to organ and site, no statistically significant differences were detected in the majority of toxicity comparisons (66.7%). For A&P, hPBT showed a more favorable toxicity profile as compared to nPBT with a higher frequency of G0 and G1 and a lower frequency of G2 and G3 events (p = 0.04), more patients with improvement (95.7% vs 70%, p = 0.023), and full resolution of toxicities (87% vs 50%, p = 0.008). Skin toxicity was unanimously milder for hPBT compared to nPBT in A&P and ST locations (p = 0.018 and p = 0.025, respectively). No significant differences in QoL were observed in 97% of comparisons for QLQ-C30 scale except for loss of appetite in H&N patients (+33.3 for nPBT and 0 for hPBT, p = 0.02) and role functioning for A&P patients (0 for nPBT vs +16.7 hPBT, p = 0.003). For QLQ-HN35, 97.9% of comparisons did not reveal significant differences, with pain as the only scale varying between the groups (-8.33 vs -25, p = 0.016). Conclusion: Hypofractionated proton therapy offers non-inferior early safety and QoL as compared to normofractionated irradiation and warrants further clinical investigation.

The Value of SSTR2 Receptor-Targeted PET/CT in Proton Irradiation of Grade I Meningioma.

Grade I meningioma is the most common intracranial tumor in adults. The standard imaging for its radiation treatment planning is MRI, and [68Ga]1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated PET/CT can further improve delineation. We investigated the impact of PET/CT on interobserver variability in identifying the tumor in 30 anonymized patients. Four radiation oncologists independently contoured residual tumor volume, first using only MRI and subsequently with the addition of PET/CT. Conformity indices (CIs) were calculated between common volumes, observer pairs and compared to the volumes previously used. Overall, 29/30 tumors (96.6%) showed [68Ga]Ga-DOTA avidity. With help of PET/CT, the participants identified six cases with new lesions not recognized in MRI, including two where new findings would critically alter the target volume used for radiation. The PET/CT-aided series demonstrated superior conformity, as compared to MRI-only between observer pairs (median CI = 0.58 vs. 0.49; p = 0.002), common volumes (CI = 0.34; vs. 0.29; p = 0.002) and matched better the reference volumes actually used for patient treatment (CI = 0.55 vs. 0.39; p = 0.008). Cis in the PET/CT-aided series were lower for meningiomas outside of the skull base (0.2 vs. 0.44; p = 0.03). We conclude that SSTR2 receptor-targeted PET/CT is a valuable tool for planning particle therapy of incompletely resected meningioma. It serves both as a workup procedure and an aid for delineation process that reduces the likelihood of marginal misses.

Comparison of clinical outcomes achieved with image-guided adaptive brachytherapy for cervix cancer using CT or transabdominal ultrasound.

PURPOSE: This study aimed to evaluate retrospectively the treatment results when using various image-guided adaptive brachytherapy treatments for cervical cancer treated by radical radiotherapy. METHODS AND MATERIALS: From 2014 to 2017, 188 patients with cervical carcinoma were treated by whole pelvic radiotherapy plus four fractions of image-guided brachytherapy. Eight patients were excluded because of missing data. Consequently, 180 patients were analyzed. Of 180 patients, 92 were treated by CT-based brachytherapy (CT-BT), and transabdominal ultrasound-based brachytherapy (TAUS-BT) was used to treat another group. The treatment results and toxicity outcomes were evaluated by comparing the image-guidance techniques. RESULTS: The mean follow-up time was 32 months (interquartile range 29.5-42 months). The mean age was 57 years (interquartile range from 50 to 65 years). In the CT-BT group, the mean cumulative doses to high-risk clinical target volume, bladder, rectum, and sigmoid were 87.2 Gy, 84.0 Gy, 68.8 Gy, and 69.8 Gy, respectively. In the TAUS-BT group, the mean cumulative doses to the cervix reference, bladder, and rectum points were 84.0 Gy, 65.5 Gy, and 74.0 Gy, respectively. There were no differences in the 2-year local control rate (p = 0.88) and disease-free survival rate (p = 0.34) in both groups. No difference in gastrointestinal and genitourinary toxicity was observed in both groups, but there was higher vaginal toxicity in the TAUS-BT group compared with the CT-BT group (p = 0.03). CONCLUSIONS: No difference in treatment results was observed between CT-based and TAUS-based approaches. However, TAUS-BT had higher vaginal toxicity in our retrospective analysis.

Salvage Mastectomy Versus Second Conservative Treatment for Second Ipsilateral Breast Tumor Event: A Propensity Score-Matched Cohort Analysis of the GEC-ESTRO Breast Cancer Working Group Database.

PURPOSE: Second conservative treatment has emerged as an option for patients with a second ipsilateral breast tumor event after conserving surgery and breast irradiation. We aimed to address the lack of evidence regarding second breast event treatment by comparing oncologic outcomes after conservative treatment or mastectomy. METHODS AND MATERIALS: Oncologic outcomes were analyzed using a propensity score-matched cohort analysis study on patients who received a diagnosis of a second breast event between January 1995 and June 2017. Patient data were collected from 15 hospitals/cancer centers in 7 European countries. Patients were offered mastectomy or lumpectomy plus brachytherapy. Propensity scores were calculated with logistic regression and multiple imputations. Matching (1:1) was achieved using the nearest neighbor method, including 10 clinical/pathologic data related to the second breast event. The primary endpoint was 5-year overall survival from the salvage surgery date. Secondary endpoints were 5-year cumulative incidence of third breast event, regional relapse and distant metastasis, and disease-free and specific survival. Complications and 5-year incidence of mastectomy were investigated in the conservative treatment cohort. RESULTS: Among the 1327 analyzed patients (mastectomy, 945; conservative treatment, 382), 754 were matched by propensity score (mastectomy, 377; conservative treatment, 377). The median follow-up was 75.4 months (95% confidence interval [CI], 65.4-83.3) and 73.8 months (95% CI, 67.5-80.8) for mastectomy and conservative treatment, respectively (P = .9). In the matched analyses, no differences in 5-year overall survival and cumulative incidence of third breast event were noted between mastectomy and conservative treatment (88% [95% CI, 83.0-90.8] vs 87% [95% CI, 82.1-90.2], P = .6 and 2.3% [95% CI, 0.7-3.9] vs 2.8% [95% CI, 0.8-4.7], P = .4, respectively). Similarly, no differences were observed for all secondary endpoints. Five-year cumulative incidence of mastectomy was 3.1% (95% CI, 1.0-5.1). CONCLUSIONS: To our knowledge, this is the largest matched analysis of mastectomy and conservative treatment combining lumpectomy with brachytherapy for second breast events. Compared with mastectomy, conservative treatment does not appear to be associated with any differences in terms of oncologic outcome. Consequently, conservative treatment could be considered a viable option for salvage treatment.

Psychometric validation of the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire Sexual Health (EORTC QLQ-SH22).

BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group developed a questionnaire to assess sexual health in patients with cancer and cancer survivors. This study evaluates the psychometric properties of the questionnaire. METHODS: The 22-item EORTC sexual health questionnaire (EORTC QLQ-SH22) was administered with the EORTC QLQ-C30 to 444 patients with cancer. The hypothesised scale structure, reliability and validity were evaluated through standardised psychometric procedures. RESULTS: The cross-cultural field study showed that the majority of patients (94.7%) were able to complete the QLQ-SH22 in less than 20 min; 89% of the study participants did not need any help to fill in the questionnaire. Multi-item multi-trait scaling analysis confirmed the hypothesised scale structure with two multi-item scales (sexual satisfaction, sexual pain) and 11 single items (including five conditional items and four gender-specific items). The internal consistency yielded acceptable Cronbach's alpha coefficients (.90 for the sexual satisfaction scale, .80 for the sexual pain scale). The test-retest correlations (Pearson's r) ranged from .70 to .93 except for the scale communication with professionals (.67) and male body image (.69). The QLQ-SH22 discriminates well between subgroups of patients differing in terms of their performance and treatment status. CONCLUSION: The study supports the reliability, the content and construct validity of the QLQ-SH22. The newly developed questionnaire is clinically applicable to assess sexual health of patients with cancer at different treatment stages and during survivorship for clinical trials and for clinical practice.

RIG-1-Like Receptor Activation Synergizes With Intratumoral Alpha Radiation to Induce Pancreatic Tumor Rejection, Triple-Negative Breast Metastases Clearance, and Antitumor Immune Memory in Mice.

Diffusing alpha-emitting radiation therapy (DaRT) employs intratumoral Ra-224-coated seeds that efficiently destroy solid tumors by slowly releasing alpha-emitting atoms inside the tumor. In immunogenic tumor models, DaRT was shown to activate systemic antitumor immunity. Agonists of the membrane-bound toll-like receptors (TLRs) enhanced these effects and led to tumor rejection. Here, we examined the combination of DaRT with agents that activate a different type of pattern recognition receptors, the cytoplasmatic RIG1-like receptors (RLRs). In response to cytoplasmatic viral dsRNA, RLRs activate an antiviral immune response that includes the elevation of antigen presentation. Thus, it was postulated that in low-immunogenic tumor models, RLR activation in tumor cells prior to the induction of their death by DaRT will be superior compared to TLR activation. Intratumoral cytoplasmatic delivery of the dsRNA mimic polyIC by polyethylenimine (PEI), was used to activate RLR, while polyIC without PEI was used to activate TLR. PolyIC(PEI) prior to DaRT synergistically retarded 4T1 triple-negative breast tumors and metastasis development more efficiently than polyIC and rejected panc02 pancreatic tumors in some of the treated mice. Splenocytes from treated mice, adoptively transferred to naive mice in combination with 4T1 tumor cells, delayed tumor development compared to naïve splenocytes. Low-dose cyclophosphamide, known to reduce T regulatory cell number, enhanced the effect of DaRT and polyIC(PEI) and led to high long-term survival rates under neoadjuvant settings, which confirmed metastasis clearance. The epigenetic drug decitabine, known to activate RLR in low doses, was given intraperitoneally prior to DaRT and caused tumor growth retardation, similar to local polyIC(PEI). The systemic and/or local administration of RLR activators was also tested in the squamous cell carcinoma (SCC) tumor model SQ2, in which a delay in tumor re-challenge development was demonstrated. We conclude that RIG-I-like activation prior to intratumoral alpha radiation may serve as a potent combination technique to reduce both tumor growth and the spread of distant metastases in low-immunogenic and metastatic tumor models.

Hyaluronic acid gel injection in rectovaginal septum reduced incidence of rectal bleeding in brachytherapy for gynecological malignancies.

PURPOSE: The purpose of this study was to report our initial clinical results of hyaluronic acid gel injection (HGI) in the rectovaginal septum (RVS) to reduce the incidence of rectal bleeding in vaginal brachytherapy for gynecologic malignancies. METHODS AND MATERIALS: Since 2008, CT based image-guided adaptive brachytherapy (IGABT) was initiated, and since 2015, HGI in the RVS was introduced in our institution. Vaginal cylinder with or without tandem or additional interstitial needles were applied for patients with gynecologic malignancies. Rectum dosimetric parameters and incidence of late rectum bleeding were compared between patients with and without HGI in the RVS. RESULTS: Between May 2008 and October 2017, 83 patients with gynecologic malignancies were treated with IGABT involving vaginal cylinder. Eleven patients who were treated for palliative intention were excluded, and 72 patients were subjected to the analysis. Of the total 72 patients 46 were with uterine cervical cancer, 19 uterine corpus cancer, five vaginal cancer, one vulvar cancer, and one ovarian cancer. Fifteen and 57 patients were irradiated with and without HGI in the RVS, respectively. With a median follow-up period of 57.7 (4.7-123.1) months, 30 (41.7%) patients suffered from radiation-related rectal bleeding. Patients with HGI in the RVS had a statistically significant lower incidence of rectal bleeding compared with those without it (13.3% vs. 49.1%, p = 0.01). CONCLUSIONS: HGI in the RVS reduced the incidence of late rectal bleeding for patients with gynecologic malignancies treated by vaginal cylinder and was not associated with HGI-procedure-related adverse events.

Radical dose escalation by high-dose-rate brachytherapy for localized prostate cancer-Significance of prostate-specific antigen nadir level within 18 months as correlation for long-term biochemical control.

PURPOSE: High-dose-rate brachytherapy (HDR-BT) for dose escalation in localized prostate cancer has been established as one standard treatment option. However, long-term results at followup (FU) ≥5 years are usually needed to ensure robustness of reported outcomes. Potential benefit of salvage therapy is, nevertheless, higher when relapse is diagnosed early. This study aimed to solve this dilemma by evaluating the prostate-specific antigen (PSA) nadir for early prediction of long-term biochemical control. METHODS AND MATERIALS: Combined pelvis-external beam radiation/HDR-BT boost to EQD2 >100 Gy (α/ß = 3) was performed in 459 consecutively treated patients. These patients with an FU ≥ 24 months were analyzed and stratified in PSA nadir (nPSA)-groups by PSA nadir within 18 months after radiotherapy (nPSA18). Kaplan-Meier/log-rank tests and Cox-regression models were used to compare the study endpoints. RESULTS: The mean FU was 77 months. A PSA nadir within 18 months (nPSA18) <0.5 ng/mL was achieved in 222 patients with median time to reach nPSA18 of 7 months. The 5-year American Society of Therapeutic Radiology and Oncology (ASTRO) biochemical control (prostate-specific antigen disease-free survival) for the nPSA18 group <0.5 ng/mL was 89% and for the group ≥ 0.5 ng/mL, it was 78.6% (p = 0.011). nPSA18 was an independent predictor of cancer-specific survival, distant metastasis-free survival, and biochemical control (ASTRO) (p = 0.026, p = 0.020, and p = 0.01, respectively). CONCLUSIONS: The present results suggest that the PSA nadir level within 18 months after radiotherapy may serve as an early parameter for long-term biochemical control according to ASTRO definitions following radical dose escalation by HDR-BT for prostate cancer. Excellent outcomes were associated with nPSA18 < 0.5 ng/mL.