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Abstract: Aims: To assess the feasibility of carbogen breathing combined with radical radiotherapy in patients with advanced head and neck cancer who are unfit to receive concomitant chemotherapy. Materials and methods: Twenty patients (median age 66 years) with advanced squamous cell carcinoma of the head and neck were treated with either concomitant boost radiotherapy (75%) or mono-fractionated radiotherapy (25%) combined with carbogen breathing. The median tumour dose was 69.5Gy. The main sites of disease were the oropharynx in 50%, the oral cavity in 15% and the hypopharynx in 30%. All but one patient had stage III (25%) or IV (70%) disease. The median follow-up for the surviving patients was 26 months (range 6–50 months). Results: Carbogen breathing was well tolerated, permitting its delivery throughout the radiotherapy course. Three patients had treatment interruption because of acute toxicities (median 15 days; range 3–30 days). Grade 3 Radiation Therapy Oncology Group acute toxicity was observed in 80% of the patients (mainly mucositis), and nutritional support was required in eight patients (40%). Grade 2 late toxicity occurred in 30%; one patient presented with grade 4 late toxicity (bone necrosis). The 2-year actuarial locoregional control for all patients and for those treated with accelerated radiotherapy was 56% and 67%, respectively. The corresponding rates for disease-free survival were 45% and 53%. Conclusions: Considering the poor results of radiotherapy alone in advanced head and neck cancer, these results suggest that carbogen breathing may be a valid alternative for patients with severe co-morbidities who are unfit to receive concomitant chemotherapy. [Copyright &y& Elsevier]

Background: A study was performed comparing volumetric modulated arcs (RA) and intensity modulation (with photons, IMRT, or protons, IMPT) radiation therapy (RT) for patients with recurrent prostate cancer after RT.Methods: Plans for RA, IMRT and IMPT were optimized for 7 patients. Prescribed dose was 56 Gy in 14 fractions. The recurrent gross tumor volume (GTV) was defined on 18F-fluorocholine PET/CT scans. Plans aimed to cover at least 95% of the planning target volume with a dose > 50.4 Gy. A maximum dose (DMax) of 61.6 Gy was allowed to 5% of the GTV. For the urethra, DMax was constrained to 37 Gy. Rectal DMedian was < 17 Gy. Results were analyzed using Dose-Volume Histogram and conformity index (CI90) parameters.Results: Tumor coverage (GTV and PTV) was improved with RA (V95% 92.6 +/- 7.9 and 83.7 +/- 3.3%), when compared to IMRT (V95% 88.6 +/- 10.8 and 77.2 +/- 2.2%). The corresponding values for IMPT were intermediate for the GTV (V95% 88.9 +/- 10.5%) and better for the PTV (V95%85.6 +/- 5.0%). The percentages of rectal and urethral volumes receiving intermediate doses (35 Gy) were significantly decreased with RA (5.1 +/- 3.0 and 38.0 +/- 25.3%) and IMPT (3.9 +/- 2.7 and 25.1 +/- 21.1%), when compared to IMRT (9.8 +/- 5.3 and 60.7 +/- 41.7%). CI90 was 1.3 +/- 0.1 for photons and 1.6 +/- 0.2 for protons. Integral Dose was 1.1 +/- 0.5 Gy*cm3 *105 for IMPT and about a factor three higher for all photon's techniques.Conclusion: RA and IMPT showed improvements in conformal avoidance relative to fixed beam IMRT for 7 patients with recurrent prostate cancer. IMPT showed further sparing of organs at risk. [ABSTRACT FROM AUTHOR]

Introduction: The NICOLAS study is the first completed single-arm phase II trial in stage III NSCLC evaluating hierarchically first the safety and then the efficacy of adding nivolumab concurrently to standard definitive concurrent chemoradiotherapy. The safety end point was reported earlier; here, we present the efficacy results., Methods: Stage IIIA-B unresectable treatment-naive patients with NSCLC received three cycles of platinum-based chemotherapy and concurrent radiotherapy (66 Gy, 33 fractions), along with nivolumab (360 mg, 3-weekly). Nivolumab was continued as monotherapy consolidation for a maximum of 1 year (480 mg, 4-weekly). The primary end point was 1-year progression-free survival (PFS), with a target improvement compared with historical data of at least 15%, from 45% to 60%. To test this efficacy hypothesis, a sample size of 74 assessable patients provided a power of 83% with a one-sided alpha of 5%., Results: A total of 79 patients were enrolled with a median follow-up of 21.0 months (interquartile range: 15.8-25.8 mo) for the primary PFS analysis. A total of 35.4% of the patients had stage IIIA, and 63.3% had stage IIIB disease. The 1-year PFS was 53.7% (95% confidence interval [CI]: 42.0%-64.0%) and the median PFS was 12.7 months (95% CI: 10.1-22.8 mo). Because 37 PFS events occurred in the first year posttreatment among the first 74 assessable patients, a 1-year PFS rate of at least 45% could not be rejected (p = 0.23). At an extended follow-up (median 32.6 mo), 37 deaths have been recorded, with a median overall survival (OS) of 38.8 months (95% CI: 26.8 mo-not estimable) and a 2-year OS rate of 63.7% (95% CI: 51.9%-73.4%). The OS of patients with stage IIIA disease was found to be significantly higher than patients with stage IIIB disease, with a 2-year OS of 81% and 56%, respectively (p = 0.037)., Conclusions: PFS and OS are arithmetically higher in studies involving the same population. However, on the basis of the formal hierarchical efficacy analysis, we could not reject that the 1-year PFS rate is at least 45%., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: Our purpose was to evaluate neurocognitive function (NCF) and clinical outcomes after early hippocampal avoidance (HA) prophylactic cranial irradiation (PCI) in limited disease (LD) small cell lung cancer (SCLC)., Methods and Materials: In a phase 2 trial, patients with LD SCLC received HA-PCI concomitant with the second cycle of chemotherapy and thoracic radiation therapy. All patients underwent objective NCF testing at baseline, 6 weeks, and 6 and 12 months after HA-PCI. NCF tests included Hopkins Verbal Learning Test Revised, Controlled Oral Word Association, and Trail Making Tests A and B. The primary endpoint was NCF decline at 6 months after HA-PCI. We assumed ≤30% of patients with no NCF decline to be unpromising. Secondary endpoints included brain metastases-free survival (BMFS), overall survival (OS), and safety of the concomitant treatment., Results: Among the 44 patients enrolled in the trial, 38 had evaluable NCF assessment at 6 months after HA-PCI. The proportion of evaluable patients showing no NCF decline at 6 and 12 months was 34.2% (90% confidence interval [CI], 21.6-48.8) and 48.5% (95% CI, 30.8-66.5), respectively. Median follow-up was 13.2 months (95% CI, 12.6-14.1). At 12 months, BMFS was 84.2% and OS was 87.7% (95% CI, 73.0-94.7). Four patients died of SCLC, 1 of respiratory failure, 1 of hemorrhage, and 1 for unknown reason. The most frequently reported grade ≥3 acute adverse events were anemia (21.4%), febrile neutropenia (19.1%), and fatigue (14.3%)., Conclusions: The proportion of patients showing no NCF decline 6 and 12 months after early HA-PCI does not appear to be better than, but rather similar to, that observed in patients receiving sequential PCI without HA. Early HA-PCI in LD SCLC is feasible, with observation of promising BMFS and OS in this selected population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: There is no general consensus on the optimal treatment for prostate cancer (PC) patients with intrapelvic nodal oligorecurrences after radical prostatectomy. Besides androgen deprivation therapy (ADT) as standard of care, both elective nodal radiotherapy (ENRT) and stereotactic body radiotherapy (SBRT) as well as salvage lymph node dissection (sLND) are common treatment options. The aim of our study was to assess decision making and practice patterns for salvage radiotherapy (RT) in this setting., Methods: Treatment recommendations from 14 Swiss radiation oncology centers were collected and converted into decision trees. An iterative process using the objective consensus methodology was applied to assess differences and consensus., Results: PSMA PET/CT was recommended by 93% of the centers as restaging modality. For unfit patients defined by age, comorbidities or low performance status, androgen deprivation therapy (ADT) alone was recommended by more than 70%. For fit patients with unfavorable tumor characteristics such as short prostate-specific antigen (PSA) doubling time or initial high-risk disease, the majority of the centers (57-71%) recommended ENRT + ADT for 1-4 lesions. For fit patients with favorable tumor characteristics, there were low levels of consensus and a wide variety of recommendations. For 1-4 nodal lesions, focal SBRT was offered by 64% of the centers, most commonly as a 5-fraction course., Conclusions: As an alternative to ADT, ENRT or SBRT for pelvic nodal oligorecurrences of PC are commonly offered to selected patients, with large treatment variations between centers. The exact number of lymph nodes had a major impact on treatment selection.

Introduction: Although salvage radiotherapy (SRT) for PSA recurrence after radical prostatectomy provides better oncological outcomes when delivered early, in the absence of detectable disease many patients are treated for macroscopic locally recurrent tumors. Due to limited data from prospective studies, we hypothesized an important variability in the SRT management of these patients. Our aim was to investigate current practice patterns of SRT for local macroscopic recurrence after radical prostatectomy., Material and Methods: A total of 14 Swiss radiation oncology centers were asked to complete a survey on treatment specifications for macroscopic locally recurrent disease including information on pretherapeutic diagnostic procedures, dose prescription, radiation delivery techniques and androgen deprivation therapy (ADT). Treatment recommendations on ADT were analyzed using the objective consensus methodology., Results: The majority of centers recommended pretreatment magnetic resonance imaging (MRI) of the pelvis and choline positron emission tomography (PET). The median prescribed dose to the prostate bed was 66 Gy (range 65-72 Gy) with a boost to the macroscopic lesion used by 79% of the centers with a median total dose of 72 Gy (range 70-80 Gy). Intensity-modulated rotational techniques were used by all centers and daily cone beam computed tomography (CT) was recommended by 43%. The use of concomitant ADT for any macroscopic recurrence was recommended by 43% of the centers while the remaining centers recommended it only for high-risk disease, which was not consistently defined., Conclusion: We observed a high variability of treatment paradigms when SRT is indicated for macroscopic local recurrences after prostatectomy. These data reflect the need for more standardized approaches and ultimately further research in this field.

Objectives: To assess the outcome of patients treated with a dose-adapted salvage radiotherapy (SRT) protocol based on an endorectal magnetic resonance imaging (erMRI) failure definition model after radical prostatectomy (RP)., Methods: We report on 171 relapsing patients after RP who had undergone an erMRI before SRT. 64 Gy were prescribed to the prostatic bed with, in addition, a boost of 10 Gy to the suspected local relapse as detected on erMRI in 131 patients (76.6%)., Results: The 3-year biochemical relapse-free survival (bRFS), local relapse-free survival, distant metastasis-free survival, cancer-specific survival, and overall survival were 64.2±4.3%, 100%, 85.2±3.2%, 100%, and 99.1±0.9%, respectively. A PSA value >1 ng/mL before salvage (P=0.006) and an absence of biochemical progression during RT (P=0.001) were both independently correlated with bRFS on multivariate analysis. No significant difference in 3-year bRFS was observed between the boost and no-boost groups (68.4±4.6% vs. 49.7±10%, P=0.251)., Conclusions: A PSA value >1 ng/mL before salvage and a biochemical progression during RT were both independently correlated with worse bRFS after SRT. By using erMRI to select patients who are most likely expected to benefit from dose-escalated SRT protocols, this dose-adapted SRT approach was associated with good biochemical control and outcome, serving as a hypothesis-generating basis for further prospective trials aimed at improving the therapeutic ratio in the salvage setting.

Uterine carcinosarcomas (UCS) are rare tumors. Consensus regarding therapeutic management in non-metastatic disease is lacking. This study reports on outcome and predictive factors when using postoperative radiotherapy. We analyzed a retrospective analysis in 124 women treated between 1987-2007 in the framework of the Rare-Cancer-Network. Median follow-up was 27 months. Postoperative pelvic EBRT was administered in 105 women (85%) and 92 patients (74%) received exclusive or additional vaginal brachytherapy. Five-year overall survival (OS), disease-free survival (DFS), cancer specific survival (CSS) and locoregional control (LRC) were 51.6% (95% CI 35-73%), 53.7% (39-71%), 58.6% (38-74%) and 48% (38-67%). Multivariate analysis showed that external beam radiation therapy (EBRT) >50Gy was an independent prognostic factor for better OS (P=0.03), CSS (P=0.02) and LRC (P=0.01). Relative risks (RR) for better OS (P=0.02), DFS (P=0.04) and LRC (P=0.01) were significantly associated with younger age (≤60 years). Higher brachytherapy (BT)-dose (>9Gy) improved DFS (P=0.04) and LRC (P=0.008). We concluded that UCS has high systemic failure rate. Local relapse was reduced by a relative risk factor of over three in all stages of diseases when using higher doses for EBRT and brachytherapy. Postoperative RT was most effective in UCS stage I/II-diseases.

Purpose: Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB., Methods and Materials: Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors., Results: The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7)., Conclusions: The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this situation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We aimed to assess the dosimetric impact of advanced delivery radiotherapy techniques using either intensity modulated x-ray beams (IMXT), volumetric modulated arc therapy (VMAT), or intensity modulated proton therapy (IMPT), for high-risk prostate cancer patients with sentinel nodes in the pararectal region. Twenty high-risk prostate cancer patients were included in a prospective trial evaluating sentinel nodes on pelvic SPECT acquisition. To be eligible for the dosimetric study, patients had to present with pararectal sentinel nodes usually not included in the clinical target volume encompassing the pelvic lymph nodes. Radiotherapy-plans including the prostate, the seminal vesicles, and the pelvic lymph nodes with the pararectal sentinel nodes were optimized for 6 eligible patients. IMXT and IMPT were delivered with 7 and 3 beams respectively and VMAT with 2 arcs. Results were assessed with Dose-Volume Histograms and predictive normal tissue complication probabilities (NTCPs) models between the three competing treatment modalities aiming to deliver a total dose of 50.4 Gy in 1.8 Gy daily fractions. Target coverage was optimized with IMPT when compared to IMXT and VMAT. Coverage of the sentinel node was slightly better with IMXT (D98% 5 57.3 ± 5.1 Gy) when compared with VMAT (D98% 5 56.2 ± 4.1 Gy). The irradiation of rectal, bladder, small bowel, and femoral heads volumes was significantly reduced with IMPT when compared to IMXT and VMAT. NTCPs rates for rectal and bladder ≥ grade-3 late toxicity were better with IMPT (0.4 ± 0.0% and 0.0 ± 0.0%) compared with IMXT (4.6 ± 3.3% and 1.4 ± 1.1%), and VMAT (4.5 ± 4.0% and 1.6 ± 1.6%), respectively. Acceptable dose-volume distributions and low rectal and urinary NTCPs were estimated to geometrically complex pelvic volumes such as the ones proposed in this study using IMXT, VMAT and IMPT. IMPT succeeded, however, to propose the best physical and biological treatment plans compared to both X-ray derived plans., (© The Author(s) 2014.)