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Simple Summary: Multiple tumor types feature frequent overexpression of somatostatin receptor type 2 (SSTR2). In addition to its well-established role in determining the primary diagnosis, a PET/CT can be helpful in the radiation treatment of these tumors. It has the potential to improve recognition of the tumor burden compared to CT or MRI alone. In a blinded comparative interobserver study, we anonymized 47 patients with various tumors with SSTR2 expression and instructed four radiation oncologists to independently contour the macroscopic tumor volume using MRI alone and subsequently with the addition of DOTA-conjugated PET/CT. This study showed that for meningioma and skull base paraganglioma (SBPGL), there was a better consensus and certainty between the observers, with the opposite trend for pituitary neuroendocrine tumors (PitNET). For PitNET and meningioma, the addition of PET/CT led to higher sensitivity between the observers compared to CT and MRI alone, suggesting the benefits of integrating DOTA-conjugated PET/CT for target definition. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Oncologic gross total resection of skull base chordoma remains elusive in many patients. Dose-escalated radiotherapy, preferably by proton therapy, is frequently used. We present the early analysis of a mono-institutional experience using proton or carbon ion therapy for skull base chordomas. Our initial 4-year clinical outcomes suggest excellent local control. Large tumor volume was related with worse local tumor control, underlining the importance of maximum debulking of large lesions. Background: Skull base chordomas are radio-resistant tumors that require high-dose, high-precision radiotherapy, as can be delivered by particle therapy (protons and carbon ions). We performed a first clinical outcome analysis of particle therapy based on the initial 4-years of operation. Methods: Between August 2017 and October 2021, 44 patients were treated with proton (89%) or carbon ion therapy (11%). Prior gross total resection had been performed in 21% of lesions, subtotal resection in 57%, biopsy in 12% and decompression in 10%. The average prescription dose was 75.2 Gy RBE in 37 fractions for protons and 66 Gy RBE in 22 fractions for carbon ions. Results: At a median follow-up of 34.3 months (range: 1–55), 2-, and 3-year actuarial local control rates were 95.5% and 90.9%, respectively. The 2-, and 3-year overall and progression-free survival rates were 97.7%, 93.2%, 95.5% and 90.9%, respectively. The tumor volume at the time of particle therapy was highly predictive of local failure (p < 0.01), and currently, there is 100% local control in patients with tumors < 49 cc. No grade ≥3 toxicities were observed. There was no significant difference in outcome or side effect profile seen for proton versus carbon ion therapy. Five patients (11.4%) experienced transient grade ≤2 radiation-induced brain changes. Conclusions: The first analysis suggests the safety and efficacy of proton and carbon ion therapy at our center. The excellent control of small to mid-size chordomas underlines the effectiveness of particle therapy and importance of upfront maximum debulking of large lesions. [ABSTRACT FROM AUTHOR]

Purpose: To establish dose-response relationships for late side effects of the rectum and bladder in cervix cancer patients after magnetic resonance image-guided adaptive brachytherapy (IGABT). Methods and Materials: A cohort of 141 patients was treated with 45 to 50.4 Gy with or without cisplatin plus 4 fractions of 7 Gy IGABT. Doses for the most exposed 2, 1, and 0.1-cm3 (D2cc, D1cc, D0.1cc) volumes of the rectum and bladder were converted into the equivalent dose in 2 Gy fractions (EQD2), using a linear quadratic model (α/β = 3 Gy). Late side effects were prospectively assessed (using late effects in normal tissues subjective, objective, management and analytic [LENT SOMA]) scales. Dose-response relationships were determined by logit analyses. Results: Eleven patients developed rectal side effects, and 23 patients had urinary side effects. A significant dose effect was found for all rectal dose-volume histogram (DVH) parameters for patients with side effect grades of 1 to 4 but was only significant for D2cc and D1cc for grades ≥2. The ED10 values for D2cc were 73 Gy for grades 1 to 4 and 78 Gy for grades 2 to 4 rectal morbidity. For bladder side effects, a significant dose effect was shown for all DVH parameters for complication grades ≥2; the respective ED10 was 101 Gy. Conclusions: Well-defined dose-response curves could be established for D2cc in the rectum and the urinary bladder. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Correlation of dosimetric parameters for MRI-based 3D treatment planning with rectoscopic findings and clinical rectal side effects. Methods and materials: Rectosigmoidoscopy and rectal morbidity assessment were performed on 35 cervical cancer patients treated with external beam radiotherapy (EBRT) and HDR-intracavitary brachytherapy (ICB). The total doses, normalised to 2Gy fractions (EQD2, α/β =3Gy), in 0.1, 1.0 and 2.0cm3 (D 0.1cc, D 1cc, D 2cc) of rectum were determined by summation of EBRT and ICB plans. Correlation analysis between clinical symptoms (LENT/SOMA) and rectoscopic changes (Vienna Rectoscopy Score, VRS) was performed. For dose–response analyses, the logit model was applied. Results: Mean follow-up was 18months. LENT/SOMA score was 1 in 4 patients, 2 in 8 patients, 4 in 1 patient. Telangiectasia was found in 26 patients (74%), five of them had ulceration corresponding to the 0.1cm3 volume (anterior wall). Mean values D 0.1cc, D 1cc, and D 2cc were 81±13, 70±9 and 66±8Gy, respectively. The ED50 values for VRS⩾3 and for LENT/SOMA⩾2 significantly increased with decreasing volumes. D 2cc was higher in patients with VRS⩾3 compared to VRS<3 (72±6 vs 62±7Gy; p <0.001) and in symptomatic vs asymptomatic patients (72±6 vs 63±8Gy; p <0.001). VRS correlated with the LENT/SOMA score. Conclusions: Rectosigmoidoscopy is sensitive in detecting mucosal changes, independent of clinical symptoms. The localization of these changes corresponds to the high dose volumes as defined by imaging. The development of mucosal and clinical changes in the rectum follows a clear dose–effect and volume–effect. DVH parameters could be established. [Copyright &y& Elsevier]

Abstract: Background and purpose: To evaluate the influence of uterus and bladder size on large and small bowel sparing with intensity modulated whole pelvic radiotherapy (IM-WPRT) in gynecologic patients. Patients and methods: Twenty patients were selected; 10 women with cervical cancer treated with definitive radiotherapy (group ‘DEF’) and 10 endometrial cancer patients treated postoperatively (group ‘POST’). Bladder, rectal wall, small (SB) and large bowel (LB) were delineated as organs at risk. A conformal four field technique and a seven field IMRT plan (prescription dose 50.4Gy) were compared in terms of DVH and various target parameters. Results: At doses between 40 and 50.4Gy statistically significant improvements (P<0.05) were observed for IM-WPRT for irradiated volume of rectal wall and bladder. In both patient groups, with IMRT the average irradiated volume of SB was reduced by a factor of 6 at 50.4Gy. This ratio was 2 for LB. In the DEF group the effect of SB-sparing with IMRT correlated with bladder size (correlation coefficient 0.70) while it did not correlate in the postoperative group. The effect of LB-sparing decreased with increasing bladder size in both groups but the impact of IMRT was larger for postoperative patients. Conclusions: IMRT significantly reduced the absolute volume of rectal wall, bladder and bowel irradiated at the prescribed dose level in gynaecologic patients. Main differences between POST and DEF patients receiving IM-WPRT were absolute volumes of LB irradiated to doses between 35 and 50Gy, suggesting an impact of intact uterus on LB volume in the pelvis. POST patients seem to benefit most from elective nodal IMRT. Bladder filling is an important co-factor influencing the benefit of IMRT with respect to OAR sparing. [Copyright &y& Elsevier]

Abstract: Background and purpose: In 1990 the skin source measuring bridge was proposed as a tool to measure (1) the distance between the interstitial implant and the overlying skin during brachytherapy boost treatment as well as (2) the distances between the lateral source end and the exit point of the guide needle. The present study reports on the clinical experience using the source skin measuring bridge with respect to incidence and grade of teleangiectasia, and their relation to source skin distances and doses. Patients and methods: Two hundred and twenty-two breast cancer patients (229 breasts) treated between 1983 and 1996 with breast conserving therapy including a brachytherapy boost were scored on the occurrence of teleangiectasia. The minimum distance between the sources (above implant and laterally) and the skin surface were measured. Results: If no bridge was used the appearance of teleangiectasia in the epiderm above the implant is 77, 63 and 50% for boost doses of 25, 20 and 15Gy, respectively. For brachytherapy boost doses of 25 and 20Gy and distances smaller than 10mm between the implant and the overlying epiderm, as determined with the skin source measuring bridge, the appearance of teleangiectasia was 78 and 46%, respectively. When respecting provisional dosimetry to spare the skin for a boost dose of 15Gy, resulting in distances between 10 and 15mm for the implant overlying skin and distances between 5 and 10mm for the lateral skin, teleangiectasia can be reduced to a minimum (6.3% above and 3.3% laterally). While in a univariate analysis several parameters (use of the bridge, boost dose, boost modality, external beam therapy modality) were predictive factors, the use of the bridge remained the only significant variable in a multivariate analysis. Conclusions: The skin source measuring bridge reduces teleangiectasia after interstitial brachytherapy boost treatment. A hypothesis made previously relating teleangiectasia and source skin distances was verified and extended. Even when 3D planning is used, the bridge allows for a provisional calculation of the security margins between source positions and the skin at the time of BT implantation to assure a correct needle positioning from the beginning, instead of correcting dwell times later on to avoid unnecessary high skin doses. [Copyright &y& Elsevier]

• In total, more than 4000 adult patients are currently treated with PT across Europe annually. • CNS and HNC tumours are the most frequently treated tumour sites. • Most centres use national or institutional guidelines for selecting patients for PT. • Treatments are usually reimbursed by national health care systems. • Most patients are included in prospective data registries and clinical trials. Major differences exist among proton therapy (PT) centres regarding PT delivery in adult cancer patient. To obtain insight into current practice in Europe, we performed a survey among European PT centres. We designed electronic questionnaires for eight tumour sites, focusing on four main topics: 1) indications and patient selection methods; 2) reimbursement; 3) on-going or planned studies, 4) annual number of patients treated with PT. Of 22 centres, 19 (86%) responded. In total, 4233 adult patients are currently treated across Europe annually, of which 46% consists of patients with central nervous system tumours (CNS), 15% head and neck cancer (HNC), 15% prostate, 9% breast, 5% lung, 5% gastrointestinal, 4% lymphoma, 0.3% gynaecological cancers. CNS are treated in all participating centres (n = 19) using PT, HNC in 16 centres, lymphoma in 10 centres, gastrointestinal in 10 centres, breast in 7 centres, prostate in 6 centres, lung in 6 centres, and gynaecological cancers in 3 centres. Reimbursement is provided by national health care systems for the majority of commonly treated tumour sites. Approximately 74% of centres enrol patients for prospective data registration programs. Phase II-III trials are less frequent, due to reimbursement and funding problems. Reasons for not treating certain tumour types with PT are lack of evidence (30%), reimbursement issues (29%) and/or technical limitations (20%). Across European PT centres, CNS tumours and HNC are the most frequently treated tumour types. Most centres use indication protocols. Lack of evidence for PT and reimbursement issues are the most reported reasons for not treating specific tumour types with PT. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To analyse dose–response relationships for local control of cervical cancer after MR image-guided brachytherapy (IGBT) based on dose–volume histogram parameters. Methods and materials: The analysis includes 141 patients with cervix cancer (stages IB–IVA) treated with 45–50.4Gy EBRT±cisplatin plus 4×7Gy IGBT. Gross tumour volume (GTV), high risk clinical target volume (HR CTV) and intermediate risk CTV (IR CTV) were delineated and DVH parameters (D90, D100) were assessed. Doses were converted to the equivalent dose in 2Gy (EQD2) using linear-quadratic model (α/β =10Gy). Groups of patients were formed according to tumour size at diagnosis (GTVD) of 2–5cm (group 1) or >5cm (2), with subgroups of the latter for HR CTV size at first IGBT 2–5cm (2a) or >5cm (2b). Dose–response dependence for local recurrence was evaluated by logit analysis. Results: Eighteen local recurrences in the true pelvis were observed. Dose–response analyses revealed a significant effect of HR CTV D100 (p =0.02) and D90 (p =0.005). The ED50-values for tumour control were 33±15Gy (D100) and 45±19Gy (D90). ED90-values were 67Gy (95% confidence interval [50;104]) and 86Gy [77;113], respectively. Conclusions: A significant dependence of local control on D100 and D90 for HR CTV was found. Tumour control rates of >90% can be expected at doses >67Gy and 86Gy, respectively. [Copyright &y& Elsevier]