Dual-tracer PET/CT protocol with [18F]FDG and [68Ga]Ga-FAPI-46 outperforms single-tracer PET/CT with [18F]FDG in different cancer types, resulting in larger functional and gross tumor volume.

PURPOSE: Fibroblast activation protein (FAP) detected by positron-emission tomography (PET) using fibroblast activation protein inhibitor (FAPI) appears to be a promising target for cancer imaging, staging, and therapy, providing added value and strength as a complement to [18F]fluorodeoxyglucose (FDG) in cancer imaging. We recently introduced a combined single-session/dual-tracer protocol with [18F]FDG and [68Ga]Ga-FAPI for cancer imaging and staging. Malignant tissue visualization and target-to-background uptake ratios (TBRs) as well as functional tumor volume (FTV) and gross tumor volume (GTV) were assessed in the present study with single-tracer [18F]FDG PET/computed tomography (CT) and with dual-tracer [18F]FDG&[68Ga]Ga-FAPI-46 PET/CT. METHODS: A total of 19 patients with head and neck and gastrointestinal cancers received initial [18F]FDG-PET/CT followed by dual-tracer PET/CT after additional injection of [68Ga]Ga-FAPI-46 during the same medical appointment (on average 13.9 ± 12.3 min after injection of [18F]FDG). Two readers visually compared detection rate of malignant tissue, TBR, FTV, and GTV for tumor and metastatic tissue in single- and dual-tracer PET/CT. RESULTS: The diagnostic performance of dual-tracer compared to single-tracer PET/CT was equal in 13 patients and superior in 6 patients. The mean TBRs of tumors and metastases in dual-tracer PET/CTs were mostly higher compared to single-tracer PET/CT using maximal count rates (CRmax). GTV and FTV were significantly larger when measured on dual-tracer compared to single-tracer PET/CT. CONCLUSION: Dual-tracer PET/CT with [18F]FDG and [68Ga]Ga-FAPI-46 showed better visualization due to a generally higher TBR and larger FTV and GTV compared to [18F]FDG-PET/CT in several tumor entities, suggesting that [68Ga]Ga-FAPI-46 provides added value in pretherapeutic staging.

Teaching in radiation oncology: now and 2025-results of a focus group with medical students.

PURPOSE: In Germany, the new Licensing Regulations for Physicians 2025 (Ärztliche Approbationsordnung, ÄApprO) define a binding legal framework on the basis of which medical faculties modernize their curricula. Since 2015, the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog 2.0., NKLM) formulates competencies and learning objectives to be achieved in the course of studies as curriculum orientation for the medical faculties. In addition, about 80% of the areas of a new core curriculum are to be made compulsory. A needs analysis in the target group of students has not yet taken place for the subject of radiation therapy (RT) or radiation oncology (RO). This study therefore surveys the experiences and requirements of students regarding medical education in RT. METHODS: Qualitative single-center study using a semistructured in-depth focus group with 11 medical students (20-26 years; 6 female, 5 male) was conducted. Brainstorming sessions were conducted in small groups and individually; oral contributions were recorded, transcribed, and analyzed using qualitative content analysis according to Mayring. Results were compared with the content of the future curriculum and reviewed for congruence with current expert recommendations of the German Society of Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO). RESULTS: The plans to develop a longitudinal and practice-oriented curriculum was positively received by students. Specifically, students wanted to introduce the basics of RT as an early link to practice in preclinical teaching units. The necessary acquisition of communicative skills should also be taught by lecturers in RO. Methodologically, regular digital survey tools for self-monitoring, discussion rooms, and problem-based learning were named. In the perception of students, the subject appears underrepresented in relation to its relevance in the multimodal therapy of oncological diseases. CONCLUSION: Results of the needs analysis for the subject of RT are consistent with ÄApprO, NKLM, and DEGRO. Moreover, they complement them and should be considered in the curriculum development of Masterplan Medical Education 2020 (Masterplan Medizinstudium 2020). The results contribute to high-quality and target-group-oriented medical training in the subject of RT, increased visibility, and thus early bonding of future physicians to RO in Germany.

Satisfaction with radiotherapy care among cancer patients treated in Germany-secondary analysis of a large multicenter study.

PURPOSE: Patient satisfaction with healthcare has been linked to clinical outcomes and regulatory agencies demand its regular assessment. Therefore, we aimed to investigate patient satisfaction with radiotherapy care and its determinants. METHODS: This is a secondary analysis of a multicenter prospective cross-sectional study. Eligible cancer patients anonymously completed questionnaires at the end of a course of radiotherapy. The outcome variable was overall patient satisfaction with radiotherapy care measured with a 10-point Likert scaled single-item. Given patient satisfaction was defined for patients scoring ≥ 8 points. Determinants of given patient satisfaction were assessed by univariable and multivariable analyses. A p-value < 0.05 was considered statistically significant. RESULTS: Out of 2341 eligible patients, 1075 participated (participation rate 46%). Data on patient satisfaction was provided by 1054 patients. There was a right-skewed distribution towards more patient satisfaction (mean = 8.8; SD = 1.68). Given patient satisfaction was reported by 85% (899/1054) of the patients. Univariable analyses revealed significant associations of lower patient satisfaction with tumor entity (rectal cancer), concomitant chemotherapy, inpatient care, treating center, lower income, higher costs, and lower quality of life. Rectal cancer as tumor entity, treating center, and higher quality of life remained significant determinants of patient satisfaction in a multivariable logistic regression. CONCLUSION: Overall patient satisfaction with radiotherapy care was high across 11 centers in Germany. Determinants of patient satisfaction were tumor entity, treating center, and quality of life. Although these data are exploratory, they may inform other centers and future efforts to maintain high levels of patient satisfaction with radiotherapy care.

Some like it cold: the cellular organization and physiological limits of cold-tolerant nitrite-oxidizing Nitrotoga.

Chemolithoautotrophic production of nitrate is accomplished by the polyphyletic functional group of nitrite-oxidizing bacteria (NOB). A widely distributed and important NOB clade in nitrogen removal processes at low temperatures is Nitrotoga, which however remains understudied due to the scarcity of cultivated representatives. Here, we present physiological, ultrastructural and genomic features of Nitrotoga strains from various habitats, including the first marine species enriched from an aquaculture system. Immunocytochemical analyses localized the nitrite-oxidizing enzyme machinery in the wide irregularly shaped periplasm, apparently without contact to the cytoplasmic membrane, confirming previous genomic data suggesting a soluble nature. Interestingly, in two strains we also observed multicellular complexes with a shared periplasmic space, which seem to form through incomplete cell division and might enhance fitness or survival. Physiological tests revealed differing tolerance limits towards dissolved inorganic nitrogen concentrations and confirmed the generally psychrotolerant nature of the genus. Moreover, comparative analysis of 15 Nitrotoga genomes showed, e.g. a unique gene repertoire of the marine strain that could be advantageous in its natural habitat and confirmed the lack of genes for assimilatory nitrite reduction in a strain found to require ammonium for growth. Overall, these novel insights largely broaden our knowledge of Nitrotoga and elucidate the metabolic variability, physiological limits and thus potential ecological roles of this group of nitrite oxidizers.

Value of PET imaging for radiation therapy.

This comprehensive review written by experts in their field gives an overview on the current status of incorporating positron emission tomography (PET) into radiation treatment planning. Moreover, it highlights ongoing studies for treatment individualisation and per-treatment tumour response monitoring for various primary tumours. Novel tracers and image analysis methods are discussed. The authors believe this contribution to be of crucial value for experts in the field as well as for policy makers deciding on the reimbursement of this powerful imaging modality.

Relevance of Candidatus Nitrotoga for nitrite oxidation in technical nitrogen removal systems.

Many biotechnological applications deal with nitrification, one of the main steps of the global nitrogen cycle. The biological oxidation of ammonia to nitrite and further to nitrate is critical to avoid environmental damage and its functioning has to be retained even under adverse conditions. Bacteria performing the second reaction, oxidation of nitrite to nitrate, are fastidious microorganisms that are highly sensitive against disturbances. One important finding with relevance for nitrogen removal systems was the discovery of the mainly cold-adapted Cand. Nitrotoga, whose activity seems to be essential for the recovery of nitrite oxidation in wastewater treatment plants at low temperatures, e.g., during cold seasons. Several new strains of this genus have been recently described and ecophysiologically characterized including genome analyses. With increasing diversity, also mesophilic Cand. Nitrotoga representatives have been detected in activated sludge. This review summarizes the natural distribution and driving forces defining niche separation in artificial nitrification systems. Further critical aspects for the competition with Nitrospira and Nitrobacter are discussed. Knowledge about the physiological capacities and limits of Cand. Nitrotoga can help to define physico-chemical parameters for example in reactor systems that need to be run at low temperatures. KEY POINTS: • Characterization of the psychrotolerant nitrite oxidizer Cand. Nitrotoga • Comparison of the physiological features of Cand. Nitrotoga with those of other NOB • Identification of beneficial environmental/operational parameters for proliferation.

Managing patient flows in radiation oncology during the COVID-19 pandemic : Reworking existing treatment designs to prevent infections at a German hot spot area University Hospital.

PURPOSE: The described work aimed to avoid cancellations of indispensable treatments by implementing active patient flow management practices and optimizing infrastructure utilization in the radiation oncology department of a large university hospital and regional COVID-19 treatment center close to the first German SARS-CoV­2 hotspot region Heinsberg in order to prevent nosocomial infections in patients and personnel during the pandemic. PATIENTS AND METHODS: The study comprised year-to-date intervention analyses of in- and outpatient key procedures, machine occupancy, and no-show rates in calendar weeks 12 to 19 of 2019 and 2020 to evaluate effects of active patient flow management while monitoring nosocomial COVID-19 infections. RESULTS: Active patient flow management helped to maintain first-visit appointment compliance above 85.5%. A slight appointment reduction of 10.3% daily (p = 0.004) could still significantly increase downstream planning CT scheduling (p = 0.00001) and performance (p = 0.0001), resulting in an absolute 20.1% (p = 0.009) increment of CT performance while avoiding overbooking practices. Daily treatment start was significantly increased by an absolute value of 18.5% (p = 0.026). Hypofractionation and acceleration were significantly increased (p = 0.0043). Integrating strict testing guidelines, a distancing regimen for staff and patients, hygiene regulations, and precise appointment scheduling, no SARS-CoV­2 infection in 164 tested radiation oncology service inpatients was observed. CONCLUSION: In times of reduced medical infrastructure capacities and resources, controlling infrastructural time per patient as well as optimizing facility utilization and personnel workload during treatment evaluation, planning, and irradiation can help to improve appointment compliance and quality management. Avoiding recurrent and preventable exposure to healthcare infrastructure has potential health benefits and might avert cross infections during the pandemic. Active patient flow management in high-risk COVID-19 regions can help Radiation Oncologists to continue and initiate treatments safely, instead of cancelling and deferring indicated therapies.

Low Temperature and Neutral pH Define "Candidatus Nitrotoga sp." as a Competitive Nitrite Oxidizer in Coculture with Nitrospira defluvii.

Nitrification is an essential process for N removal in activated sludge to avoid toxicity of ammonium and nitrite. Besides Nitrospira, "Candidatus Nitrotoga" has been identified as a key nitrite-oxidizing bacterium (NOB) performing the second step of nitrification, nitrite oxidation to nitrate, in wastewater treatment plants (WWTPs). However, the driving forces for the dominance of Nitrotoga in certain plants have often remained unclear and could not be explained solely by temperature effects. In this study, we characterized the physiology of the ammonium-dependent Nitrotoga sp. BS with regard to temperature and pH variations and evaluated its competitiveness against Nitrospira defluvii Both NOB originated from the same WWTP and shared a comparable pH optimum of 7.3. Based on these results, coculturing experiments with these NOB were performed in batch reactors operated at either 17°C or 22°C to compare their abundances under optimal (pH 7.4) or suboptimal (pH 6.4) conditions using 1 mM nitrite. As revealed by quantitative PCR (qPCR), fluorescence in situ hybridization (FISH), and 16S amplicon sequencing, Nitrotoga sp. BS was clearly favored by its optimal growth parameters and dominated over Ns. defluvii at pH 7.4 and 17°C, whereas a pH of 6.4 was more selective for Ns. defluvii Our synthetic communities revealed that niche differentiation of NOB is influenced by a complex interaction of environmental parameters and has to be evaluated for single species.IMPORTANCE "Ca. Nitrotoga" is a NOB of high environmental relevance, but physiological data exist for only a few representatives. Initially, it was detected in specialized niches of low temperature and low nitrite concentrations, but later on, its ubiquitous distribution revealed its critical role for N removal in engineered systems like WWTPs. In this study, we analyzed the competition between Nitrotoga and Nitrospira in bioreactors and identified conditions where the K strategist Ns. defluvii was almost replaced by Nitrotoga sp. BS. We show that the pH value is an important factor that regulates the composition of the nitrite-oxidizing enrichment with a dominance of Nitrotoga sp. BS versus Ns. defluvii at a neutral pH of 7.4 in combination with a temperature of 17°C. The physiological diversity of novel Nitrotoga cultures improves our knowledge about niche differentiation of NOB with regard to functional nitrification under suboptimal conditions.

Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [177Lu]Lu-PSMA-617.

PURPOSE: Up to 30% of patients with castration-resistant prostate cancer (CRPC) do not show any response to the first cycle of radioligand therapy (RLT) with [177Lu]Lu-PSMA-617 (Lu-PSMA). We evaluated patient response to the second and third cycles of RLT in patients that underwent at least three cycles. The second aim of this study was to calculate the median overall survival (OS) of responders and non-responders after the first cycle and after all three cycles of RLT. METHODS: CRPC patients were treated with Lu-PSMA, with a median interval of 8 weeks between each cycle. The tumour marker prostate-specific antigen (PSA) was used as the marker for response evaluation. RESULTS: Fifty-two patients underwent a total of 190 cycles of RLT (3-6 cycles per patient). Of these, 80.8% showed a decline in PSA 2 months after the first cycle, with 44.2% showing a PSA decline of ≥50%. When compared to baseline PSA, 73.1% showed a PSA decline after the third cycle. 50% of patients that did not show any response to the first cycle also did not respond to the second and third cycles. The median OS was 60 weeks in all patients. The median OS was significantly longer for patients that showed any PSA decline after the first cycle compared to patients without PSA decline (68 vs. 33 weeks). There was a significant difference in median OS between responders and non-responders for a change in PSA after the third cycle compared to baseline PSA. CONCLUSION: Patients with a positive response to RLT, regardless of the rate of decline, had a significantly longer median OS. Of the patients that did not show any response to the first cycle, 50% responded to the second or third cycles.

Relative Abundance of Nitrotoga spp. in a Biofilter of a Cold-Freshwater Aquaculture Plant Appears To Be Stimulated by Slightly Acidic pH.

The functioning of recirculation aquaculture systems (RAS) is essential to maintain water quality for fish health, and one crucial process here is nitrification. The investigated RAS was connected to a rainbow trout production system and operated at an average temperature of 13°C and pH 6.8. Community analyses of the nitrifying biofilm revealed a coexistence of Nitrospira and Nitrotoga, and it is hypothesized that a slightly acidic pH in combination with lower temperatures favors the growth of the latter. Modification of the standard cultivation approach toward lower pH values of 5.7 to 6.0 resulted in the successful enrichment (99% purity) of Nitrotoga sp. strain HW29, which had a 16S rRNA sequence similarity of 99.0% to Nitrotoga arctica. Reference cultures of Nitrospira defluvii and the novel Nitrotoga sp. HW29 were used to confirm differentiation of these nitrite oxidizers in distinct ecological niches. Nitrotoga sp. HW29 revealed pH and temperature optima of 6.8 and 22°C, respectively, whereas Nitrospira defluvii displayed the highest nitrite oxidation rate at pH 7.3 and 32°C. We report here the occurrence of Nitrotoga as one of the main nitrite-oxidizing bacteria in freshwater aquaculture systems and indicate that a slightly acidic pH, in addition to temperatures below 20°C, can be applied as a selective isolation criterion for this microorganism.

Impact of FAPI-46/dual-tracer PET/CT imaging on radiotherapeutic management in esophageal cancer.

BACKGROUND: Fibroblast activation protein (FAP) is expressed in the tumor microenvironment (TME) of various cancers. In our analysis, we describe the impact of dual-tracer imaging with Gallium-68-radiolabeled inhibitors of FAP (FAPI-46-PET/CT) and fluorodeoxy-D-glucose (FDG-PET/CT) on the radiotherapeutic management of primary esophageal cancer (EC). METHODS: 32 patients with EC, who are scheduled for chemoradiation, received FDG and FAPI-46 PET/CT on the same day (dual-tracer protocol, 71%) or on two separate days (29%) We compared functional tumor volumes (FTVs), gross tumor volumes (GTVs) and tumor stages before and after PET-imaging. Changes in treatment were categorized as "minor" (adaption of radiation field) or "major" (change of treatment regimen). Immunohistochemistry (IHC) staining for FAP was performed in all patients with available tissue. RESULTS: Primary tumor was detected in all FAPI-46/dual-tracer scans and in 30/32 (93%) of FDG scans. Compared to the initial staging CT scan, 12/32 patients (38%) were upstaged in nodal status after the combination of FDG and FAPI-46 PET scans. Two lymph node metastases were only visible in FAPI-46/dual-tracer. New distant metastasis was observed in 2/32 (6%) patients following FAPI-4 -PET/CT. Our findings led to larger RT fields ("minor change") in 5/32 patients (16%) and changed treatment regimen ("major change") in 3/32 patients after FAPI-46/dual-tracer PET/CT. GTVs were larger in FAPI-46/dual-tracer scans compared to FDG-PET/CT (mean 99.0 vs. 80.3 ml, respectively (p < 0.001)) with similar results for nuclear medical FTVs. IHC revealed heterogenous FAP-expression in all specimens (mean H-score: 36.3 (SD 24.6)) without correlation between FAP expression in IHC and FAPI tracer uptake in PET/CT. CONCLUSION: We report first data on the use of PET with FAPI-46 for patients with EC, who are scheduled to receive RT. Tumor uptake was high and not depending on FAP expression in TME. Further, FAPI-46/dual-tracer PET had relevant impact on management in this setting. Our data calls for prospective evaluation of FAPI-46/dual-tracer PET to improve clinical outcomes of EC.

First Clinical Experience With [68Ga]Ga-FAPI-46-PET/CT Versus [18F]F-FDG PET/CT for Nodal Staging in Cervical Cancer.

INTRODUCTION: In several solid tumors, fibroblast activation protein (FAP) is overexpressed by cancer-associated fibroblasts in the tumor microenvironment. Preliminary evidence suggests that detection and staging are feasible with PET/CT imaging using [68Ga]-radiolabeled inhibitors of FAP also in cervical cancer (CC). Our study aims to explore the accuracy of [68Ga]Ga-fibroblast activation protein inhibitor (FAPI)-46 PET/CT and [18F]F-FDG PET/CT compared with histopathological results of surgical lymph node (LN) staging before primary chemoradiation. METHODS: Seven consecutive women with treatment-naive and biopsy-proven locally advanced CC underwent both whole-body [68Ga]Ga-FAPI-46- and [18F]F-FDG PET/CT, for imaging nodal staging before systematic laparoscopic lymphadenectomy of the pelvic and para-aortic region. Location and number of suspicious LNs in PET imaging were recorded and compared with the results of histopathological analysis, including immunohistochemical staining for FAP. RESULTS: All 7 patients had focal uptake above background in their tumor lesions in [68Ga]Ga-FAPI-46 PET/CT. [68Ga]Ga-FAPI-46 PET/CT showed a higher tumor-to-background ratio (TBR) in primary tumor as well as in LN metastasis. Median TBRmax values using liver were 32.02 and 5.15 for [68Ga]Ga-FAPI-46 PET/CT and [18F]F-FDG PET/CT, respectively. Median TBRmax using blood pool was 18.45 versus 6.85 for [68Ga]Ga-FAPI-46 PET/CT and [18F]F-FDG PET/CT, respectively. Higher TBR also applies for nodal metastasis: TBRmax was 14.55 versus 1.39 (liver) and 7.97 versus 1.8 (blood pool) for [68Ga]Ga-FAPI-46 PET/CT and [18F]F-FDG PET/CT, respectively. Overall, [68Ga]Ga-FAPI-46 PET/CT detected more lesions compared with [18F]F-FDG PET/CT. Following surgical staging, a total of 5 metastatic LNs could be pathologically confirmed, of which 2 and 4 were positive by [18F]F-FDG PET/CT and [68Ga]Ga-FAPI-46 PET/CT, respectively. CONCLUSION: [68Ga]Ga-FAPI-46 PET/CT seems useful to improve detection of nodal metastasis in patients with CCs. Future studies should aim to compare [68Ga]Ga-FAPI-46 PET/CT to surgical staging of pelvic and para-aortic LNs in patients with locally advanced CC.

Financial toxicity in cancer patients undergoing radiotherapy in a universal health care system - A prospective multicenter study of 1075 patients.

PURPOSE: To establish and confirm prevalence as well as risk factors of financial toxicity in a large national cohort of cancer patients undergoing radiotherapy in a universal health care system. METHODS: We conducted a prospective cross-sectional study offering a patient-reported questionnaire to all eligible cancer patients treated with radiotherapy in 11 centers in Germany during 60 consecutive days. The four-point subjective financial distress question of the EORTC QLQ-C30 was used as a surrogate for financial toxicity. Confirmatory hypothesis testing evaluated the primary study outcomes: overall prevalence of financial toxicity and its association with predefined risk factors. P-values < 0.05 were considered statistically significant. RESULTS: Of 2341 eligible patients, 1075 (46%) participated. The prevalence of subjective financial distress (=any grade higher than not present) was 41% (438/1075) exceeding the hypothesized range of 26.04-36.31%. Subjective financial distress was felt "A little" by 26% (280/1075), "Quite a bit" by 11% (113/1075) and "Very much" by 4% (45/1075) of the patients. Lower household income, lower global health status/ quality of life, higher direct costs and higher loss of income significantly predicted higher subjective financial distress per ordinal regression and confirmed these risk factors. Higher psychosocial distress and lower patient satisfaction were significantly associated with higher subjective financial distress in an exploratory ordinal regression model. CONCLUSION: The overall prevalence of financial toxicity was higher than anticipated, although reported at low or moderate degrees by most affected patients. As we confirmed risk factors associated with financial toxicity, patients at risk should be addressed early for potential support.

Psychosocial distress in cancer patients undergoing radiotherapy: a prospective national cohort of 1042 patients in Germany.

PURPOSE: Psychosocial distress is common among cancer patients in general, but those undergoing radiotherapy may face specific challenges. Therefore, we investigated the prevalence and risk factors for distress in a large national cohort. METHODS: We performed a secondary analysis of a multicenter prospective cross-sectional study which surveyed cancer patients at the end of a course of radiotherapy using a patient-reported questionnaire. Distress was measured with the distress thermometer (DT), using a cut-off of ≥ 5 points for clinically significant distress. Univariate analyses and multivariate multiple regression were used to assess associations of distress with patient characteristics. A two-sided p-value < 0.05 was considered statistically significant. RESULTS: Out of 2341 potentially eligible patients, 1075 participated in the study, of which 1042 completed the DT. The median age was 65 years and 49% (511/1042) of patients were female. The mean DT score was 5.2 (SD = 2.6). Clinically significant distress was reported by 63% (766/1042) of patients. Of the patient characteristics that were significantly associated with distress in the univariate analysis, a lower level of education, a higher degree of income loss, lower global quality of life, and a longer duration of radiotherapy in days remained significantly associated with higher distress in the multivariate analysis. Yet effect sizes of these associations were small. CONCLUSION: Nearly two in three cancer patients undergoing radiotherapy reported clinically significant distress in a large multicenter cohort. While screening and interventions to reduce distress should be maintained and promoted, the identified risk factors may help to raise awareness in clinical practice. TRIAL REGISTRY IDENTIFIER: DRKS: German Clinical Trial Registry identifier: DRKS00028784.

Dose-escalated re-irradiation improves outcome in locally recurrent head and neck cancer - Results of a large multicenter analysis.

To determine efficacy and prognostic parameters of definitive re-irradiation of locoregionally recurrent squamous cell carcinoma of the head and neck (HNSCC). MATERIALS AND METHODS: Patients with locoregionally recurrent or second primary HNSCC undergoing re-irradiation with modern radiotherapy technique were eligible for this multicentric retrospective analysis. Main endpoints were overall survival (OS), progression-free survival (PFS) and locoregional control (LC). Univariate analyses were performed using the Kaplan Meier Method (log-rank). For multivariable analysis, Cox regression was used. RESULTS: A total of 253 patients treated between 2009 and 2020 at 16 university hospitals in Germany were included. The median follow up was 27.4 months (range 0.5-130). The median OS and PFS were 13.2 (CI: 10.7 - 15.7) months and 7.9 (CI: 6.7 - 9.1) months, respectively, corresponding to two-year OS and PFS rates of 29 % and 19 %. Rates of locoregional progression and "in-field-failure" were 62 % and 51 % after two years. Multivariable Cox regression analysis identified good ECOG performance status and high radiation dose as independent prognostic parameters for OS. Doses above 50 Gy (EQD2) achieved longer median OS of 17.8 months (vs 11.7 months, p < 0.01) and longer PFS of 9.6 months (vs 6.8 months, p < 0.01). In addition, there was a trend for worse survival in patients with tracheostomy (multivariable, p = 0.061). Concomitant systemic therapy did not significantly impact PFS or OS. CONCLUSION: Re-irradiation of locally recurrent or second primary HNSCC is efficient, especially if doses above 50 Gy (EQD2) are delivered. ECOG performance score was the strongest prognostic parameter for OS and PFS.

Dual-Tracer PET/CT Protocol with [18F]-FDG and [68Ga]Ga-FAPI-46 for Cancer Imaging: A Proof of Concept.

Imaging studies with PET tracers acting as fibroblast activation protein inhibitors (FAPIs) show promising results that could usefully complement [18F]-FDG in cancer imaging. Methods: All patients received [18F]-FDG PET/CT and dual-tracer PET/CT after an additional injection of [68Ga]Ga-FAPI-46 after the [18F]-FDG PET/CT. Two readers visually compared detection rate and analyzed target-to-background ratios for tumor and metastatic tissue in single- and dual-tracer PET/CT. Results: Detection rate in dual-tracer PET/CT was visually as good as that in single-tracer PET/CT in 4 patients and superior in 2 patients, whereas target-to-background ratios were significantly higher in dual-tracer PET/CT. Conclusion: Dual-tracer [18F]-FDG/[68Ga]Ga-FAPI-46 PET/CT within a single session is feasible and has potential. The dual-tracer approach may have superior sensitivity to [18F]-FDG PET/CT alone without compromising individual assessment of either scan.

Chemoradiation for elderly patients (≥ 65 years) with esophageal cancer: a retrospective single-center analysis.

BACKGROUND: Present studies on the efficacy and safety of curative chemoradiation therapy (CRT) with esophageal cancer reflect heterogenous results especially in elderly patients. The aim of this study was to evaluate the toxicity and efficacy of CRT in patients ≥ 65 years. In a cohort, the focus centered around treatment-related toxicity (CTCAE Grade > 3), overall survival as well as progression free survival, comparing these rates in-between patients older than 70 years to those younger than 70 years. METHODS: A total of 67 patients older than 65 years (34 (50.7%) were older than 70 years) met the inclusion criteria for retrospective analysis (period from January 2013 to October 2017). Treatment consisted of radiotherapy and chemotherapy with carboplatin/paclitaxel or fluorouracil (5-FU)/cisplatin with the intention of neoadjuvant or definite chemoradiation. A sum of 67 patients received CRT (44 (65.6%) patients in neoadjuvant, 23 (34.4%) in definite intent). Of these, 22 and 12 patients were older than 70 years (50% and 52.2% in both treatment groups, respectively). Median age was 71 years and patients had a good physical performance status (ECOG 0: 57.6%, ECOG 1: 27.3%). Median follow-up was 24 months. Most patients had advanced tumour stages (T3 stage: n = 51, 79.7%) and nodal metastasis (N1 stage: n = 54, 88.5%). A subgroup comparison was conducted between patients aged ≤ 70 years and > 70 years. RESULTS: In severe (CTCAE Grade 3-5) toxicities (acute and late), no significant differences were observed between both patient groups (< 70 years vs. > 70 years). 21% had acute grade 3 events, 4 patients (4%) had grade 4 events, and two patients (3%) had one grade 5 event. Late toxicity after CRT was grade 1 in 13 patients (22%), grade 2 in two (3%), grade 3 in two (3%), grade 4 in four (7%), and grade 5 in one (2%). Median overall survival (OS) of all patients was 30 months and median progression-free survival (PFS) was 16 months. No significant differences were seen for OS (32 months vs. 25 months; p = 0.632) and PFS (16 months vs. 12 months; p = 0.696) between older patients treated with curative intent and younger ones. Trimodal therapy significantly prolonged both OS and PFS (p = 0.005; p = 0.018), regardless of age. CONCLUSION: CRT in elderly patients (≥ 65 years) with esophageal cancer is feasible and effective. Numbers for acute and late toxicities can be compared to cohorts of younger patients (< 65 years) with EC who received the same therapies. Age at treatment initiation alone should not be the determining factor. Instead, functional status, risk of treatment-related morbidities, life expectancy and patient´s preferences should factor into the choice of therapy.

The Role of Age and Comorbidities in Esophagogastric Cancer Chemoradiation of the Frail Elderly (>70 Years): An Analysis from a Tertiary High Volume-Center

Elderly patients > 70 years of age with esophageal cancer (EC) represent a challenging group as frailty and comorbidities need to be considered. The aim of this retrospective study was to evaluate the efficacy and side effects of curative chemoradiation therapy (CRT) with regard to basic geriatric screening in elderly patients in order to elucidate prognostic factors. Thirty-four elderly patients > 70 years with EC treated at our cancer center between May 2014 and October 2018 fulfilled the selection criteria for this retrospective analysis. Treatment consisted of intravenous infusion of carboplatin/paclitaxel or fluorouracil (5-FU)/cisplatin with the intention of neoadjuvant or definite chemoradiation. Clinicopathological data including performance status (ECOG), (age-adjusted) Charlson comorbidity index (CCI), Frailty-scale by Fried, Mini Nutritional Assessment Short Form, body mass index, C-reactive protein to albumin ratio, and treatment-related toxicity (CTCAE) were assessed. Data were analyzed as predictors of overall survival (OS) and progression-free survival (PFS). All patients (ten female, 24 male) received combined CRT (22 patients in neoadjuvant, 12 patients in definite intent). Median age was 75 years and the ECOG index between 0 and 1 (52.9% vs. 35.3%); four patients were rated as ECOG 3 (11.8%). Median follow-up was 24 months. Tumors were mainly located in the lower esophagus or esophagogastric-junction with an T3 stage (n = 25; 75.8%) and N1 stage (n = 28; 90.3%). 15 patients (44.1%) had SCC, 19 patients (55.9%) AC. 26 of the patients (76.5%) were scored as prefrail and 50% were in risk for malnutrition (n = 17). In relation to the BMI, ten patients (29.4%) were ranked as overweight, and 15 patients were presented in a healthy state of weight (44.1%). Grade 3 acute toxicity (or higher) occured in nine cases (26.5%). Most of the patients did not show any late toxicities (66.7%). Trimodal therapy provides a significant prolonged OS (p = 0.049) regardless of age, but without impact on PFS. Our analysis suggests that chemoradiation therapy is feasible for elderly patients (>70 years) with tolerable toxicity. Trimodal therapy of EC shows a positive effect on OS and PFS. Further studies are needed to elucidate benefitting subgroups within the elderly. In addition to age, treatment decisions should be based on performance status, nutritional condition and multidisciplinary validated geriatric screening tools.