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Monitoring of radiochemotherapy (RCX) in patients with glioblastoma is difficult because unspecific alterations in magnetic resonance imaging with contrast enhancement can mimic tumor progression. Changes in tumor to brain ratios (TBRs) in positron emission tomography (PET) using O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) after RCX with temozolomide of patients with glioblastoma have been shown to be valuable parameters to predict survival. The kinetic behavior of 18F-FET in the tumors is another promising parameter to analyze tumor metabolism. In this study, we investigated the predictive value of dynamic 18F-FET PET during RCX of glioblastoma. Time-activity curves (TACs) of 18F-FET uptake of 25 patients with glioblastoma were evaluated after surgery (FET-1), early (7-10 days) after completion of RCX (FET-2), and 6 to 8 weeks later (FET-3). Changes in the time to peak (TTP) and the slope of the TAC (10-50 minutes postinjection) were analyzed and related to survival. Changes in kinetic parameters of 18F-FET uptake after RCX showed no relationship with survival time. In contrast, the high predictive value of changes of TBR to predict survival was confirmed. We conclude that dynamic 18F-FET PET does not provide additional prognostic information during RCX. Static 18F-FET PET imaging (20-40 minutes postinjection) appears to be sufficient for this purpose and reduces costs. [ABSTRACT FROM AUTHOR]

PET using O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) allows improved imaging of tumor extent of cerebral gliomas in comparison to MRI. In experimental brain infarction and hematoma, an unspecific accumulation of 18F-FET has been detected in the area of reactive astrogliosis which is a common cellular reaction in the vicinity of cerebral gliomas. The aim of this study was to investigate possible 18F-FET uptake in the area of reactive gliosis in the vicinity of untreated and irradiated rat gliomas. Methods: F98-glioma cells were implanted into the caudate nucleus of 33 Fisher CDF rats. Sixteen animals remained untreated and in 17 animals the tumor was irradiated by Gamma Knife 5–8days after implantation (2/50Gy, 3/75Gy, 6/100Gy, 6/150Gy). After 8–17 days of tumor growth the animals were sacrificed following injection of 18F-FET. Brains were removed, cut in coronal sections and autoradiograms of 18F-FET distribution were produced and compared with histology (toluidine blue) and reactive astrogliosis (GFAP staining). 18F-FET uptake in the tumors and in areas of reactive astrocytosis was evaluated by lesion to brain ratios (L/B). Results: Large F98-gliomas were present in all animals showing increased 18F-FET-uptake which was similar in irradiated and non-irradiated tumors (L/B: 3.9±0.8 vs. 4.0±1.3). A pronounced reactive astrogliosis was noted in the vicinity of all tumors that showed significantly lower 18F-FET-uptake than the tumors (L/B: 1.5±0.4 vs. 3.9±1.1). The area of 18F-FET-uptake in the tumor was congruent with histological tumor extent in 31/33 animals. In 2 rats irradiated with 150Gy, however, high 18F-FET uptake was noted in the area of astrogliosis which led to an overestimation of the tumor size. Conclusions: Reactive astrogliosis in the vicinity of gliomas generally leads to only a slight 18F-FET-enrichment that appears not to affect the correct definition of tumor extent for treatment planning. [ABSTRACT FROM AUTHOR]

Purpose: Early detection of treatment response in glioma patients after radiochemotherapy (RCX) is uncertain because treatment-related contrast enhancement in magnetic resonance imaging can mimic tumor progression. Positron emission tomography (PET) using the amino acid tracer [18F]fluoroethyltyrosine (FET) seems to be a promising tool for treatment monitoring. The aim of this prospective study was to evaluate the prognostic value of early changes of FET uptake after postoperative RCX in glioblastomas. Methods and Materials: Twenty-two patients with glioblastoma were treated by surgery and subsequent RCX (whole dose 60–72 Gy). The FET-PET studies were performed before RCX, 7–10 days and 6–8 weeks after completion of RCX. Early treatment response in PET was defined as a decrease of the maximal tumor-to-brain ratio (TBRmax) of FET uptake after RCX of more than 10%. The prognostic value of early changes of FET uptake after RCX was evaluated using Kaplan-Maier estimates for median disease-free survival and overall survival. Results: The median overall and disease-free survival of the patients was 14.8 and 7.8 months. There were 16 early responders in FET-PET (72.7%) and 6 nonresponders (27.3%). Early PET responders had a significantly longer median disease-free survival (10.3 vs. 5.8 months; p < 0.01) and overall survival (“not reached” vs. 9.3 months; p < 0.001). No statistically significant differences between the patient subgroups were found concerning the defined prognostic parameters. Conclusions: FET-PET is a sensitive tool to predict treatment response in patients with glioblastomas at an early stage after RCX. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Resection is considered as essential for the efficacy of modern adjuvant treatment of glioblastoma multiforme (GBM). Previous studies have indicated that amino acid PET is more specific than contrast enhancement on MRI for detecting residual tumor tissue after surgery. In a prospective study we investigated the prognostic impact of postoperative tumor volume and tumor/brain ratios (TBR) in PET using O-(2-[18F]fluoroethyl)-l-tyrosine (FET) in comparison with MRI. Materials and methods: Forty-four patients with GBM were investigated by FET PET and MRI after surgery. Tumor volume in FET PET with a tumor/brain ratio (TBR)>1.6 and a TBR>2, mean and maximum TBR and gadolinium contrast-enhancement on MRI (Gd-volume) were determined. Thereafter patients received a fractionated radiotherapy with concomitant temozolomide (RCX). The median follow-up was 15.4 (3–35) months. The prognostic value of postoperative residual tumor volume in FET PET, TBRmean, TBRmax and Gd-volume was evaluated using Kaplan–Maier estimates for disease-free survival (DFS) and overall survival (OS). Results: Postoperative tumor volume in FET PET had a significant independent influence on OS and DFS (OS 20.0 vs. 6.9months; DFS 9.6 vs. 5.1months, p <0.001; cut-off 25ml). Similar results were observed when a TBR⩾2 (cut-off 10ml) was used to define the tumor volume in 18F-FET PET. The TBRmean and TBRmax of FET uptake had a significant influence on DFS (p <0.05). Gd-volume in MRI had significant effect on OS and DFS in the univariate analysis. No independent significant influence in OS or DFS could be observed for Gd-volume in MRI. Conclusions: Our data indicate that the tumor volume in FET PET after surgery of GBM has a strong prognostic impact for these patients. FET PET appears to be helpful to determine the residual tumor volume after surgery of GBM and may serve as a valuable tool for optimal planning of radiation treatment. [Copyright &y& Elsevier]

Background: The present study was conducted to analyze the value of ([18F] fluoromisonidazole (FMISO) and [18F]-2-fluoro-2'-deoxyglucose (FDG) PET as well as color pixel density (CPD) and tumor perfusion (TP) assessed by color duplex sonography (CDS) for determination of therapeutic relevant hypoxia. As a standard for measuring tissue oxygenation in human tumors, the invasive, computerized polarographic needle electrode system (pO2 histography) was used for comparing the different non invasive measurements. Methods: Until now a total of 38 Patients with malignancies of the head and neck were examined. Tumor tissue pO2 was measured using a pO2-histograph. The needle electrode was placed CTcontrolled in the tumor without general or local anesthesia. To assess the biological and clinical relevance of oxygenation measurement, the relative frequency of pO2 readings, with values ≤ 2.5, ≤ 5.0 and ≤ 10.0 mmHg, as well as mean and median pO2 were stated. FMISO PET consisted of one static scan of the relevant region, performed 120 min after intravenous administration. FMISO tumor to muscle ratios (FMISOT/M) and tumor to blood ratios (FMISOT/B) were calculated. FDG PET of the lymph node metastases was performed 71 ± 17 min after intravenous administration. To visualize as many vessels as possible by CDS, a contrast enhancer (Levovist®, Schering Corp., Germany) was administered. Color pixel density (CPD) was defined as the ratio of colored to grey pixels in a region of interest. From CDS signals two parameters were extracted: color hue - defining velocity (v) and color area - defining perfused area (A). Signal intensity as a measure of tissue perfusion (TP) was quantified as follows: TP ≤ vmean × Amean. Results: In order to investigate the degree of linear association, we calculated the Pearson correlation coefficient. Slight (∣r∣ > 0.4) to moderate (∣r∣ > 0.6) correlation was found between the parameters of pO2 polarography (pO2 readings with values ≤ 2.5, ≤ 5.0 and ≤ 10.0 mmHg, as well as median pO2), CPD and FMISOT/M. Only a slight correlation between TP and the fraction of pO2 values ≤ 10.0 mmHg, median and mean pO2 could be detected. After exclusion of four outliers the absolute values of the Pearson correlation coefficients increased clearly. There was no relevant association between mean or maximum FDG uptake and the different polarographic- as well as the CDS parameters. Conclusion: CDS and FMISO PET represent different approaches for estimation of therapy relevant tumor hypoxia. Each of these approaches is methodologically limited, making evaluation of clinical potential in prospective studies necessary. [ABSTRACT FROM AUTHOR]

Background: Experimental and clinical evidence suggest that hypoxia in solid tumours reduces their sensitivity to conventional treatment modalities modulating response to ionizing radiation or chemotherapeutic agents. The aim of the present study was to show the feasibility of determining radiotherapeutically relevant hypoxia and early tumour response by ([18F] Fluoromisonidazole (FMISO) and [18F]-2-fluoro-2'-deoxyglucose (FDG) PET. Methods: Eight patients with non-small-cell lung cancer underwent PET scans. Tumour tissue oxygenation was measured with FMISO PET, whereas tumour glucose metabolism was measured with FDG PET. All PET studies were carried out with an ECAT EXACT 922/47® scanner with an axial field of view of 16.2 cm. FMISO PET consisted of one static scan of the relevant region, performed 180 min after intravenous administration of the tracer. The acquisition and reconstruction parameters were as follows: 30 min emission scanning and 4 min transmission scanning with 68-Ge/68-Ga rod sources. The patients were treated with chemotherapy, consisting of 2 cycles of gemcitabine (1200 mg/m2) and vinorelbine (30 mg/m2) followed by concurrent radio- (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine (300-500 mg/m2) every two weeks. FMISO PET and FDG PET were performed in all patients 3 days before and 14 days after finishing chemotherapy. Results: FMISO PET allowed for the qualitative and quantitative definition of hypoxic sub-areas which may correspond to a localization of local recurrences. In addition, changes in FMISO and FDG PET measure the early response to therapy, and in this way, may predict freedom from disease, as well as overall survival. Conclusion: These preliminary results warrant validation in larger trials. If confirmed, several novel treatment strategies may be considered, including the early use of PET to evaluate the effectiveness of the selected therapy. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: The aim of the study was to evaluate the impact of a dose escalation to an 18F-choline PET-CT defined simultaneous integrated boost (IB) on the dose distribution and changes of the equivalent uniform dose (EUD). Materials and methods: PET-CT was performed in 12 consecutive patients for treatment planning. An intraprostatic lesion was defined by a tumour-to-background uptake value ratio >2 (GTVPET). Dose escalation was focused only on the intraprostatic lesion. Two comparisons were evaluated: whole prostate irradiation to 76Gy±boost to 80Gy (C1) and whole prostate irradiation to 66.6Gy±boost to 83.25Gy (C2). Results: PTV/GTVPET +margins were covered by a mean EUD of 75.9/76.1Gy vs. 77.1/80.1Gy (C1) and 66.5/66.2Gy vs. 71.1/82.9Gy (C2) (p <0.01, respectively). Concerning the organs at risk, EUD increased slightly with an additional boost (mean EUD for bladder: C1 53.2Gy vs. 53.8Gy; C2 43.0Gy vs. 45.1Gy; for rectum: C1 52.0Gy vs. 52.6Gy; C2 43.0Gy vs. 45.4Gy; p <0.01, respectively). The distance to the organs at risk had a significant impact on the respective maximum doses in the treatment plans with IB. Conclusions: Treatment planning with IB allows an individually adapted dose escalation. The therapeutic ratio can be improved by a considerable dose escalation to the macroscopic tumour, but only minor EUD changes to the bladder and rectum. [Copyright &y& Elsevier]

Prostate cancer is the most frequent cancer in men. For localized prostate cancer, surgery and radiotherapy are the standard treatment, with active surveillance also used in low-risk cases. For advanced/metastatic disease, androgen deprivation treatment is carried out. Further options include inhibitors of the androgen receptor axis and taxane-based chemotherapy. The avoidance of side effects should be considered, e.g., by dose adjustment. New options include poly(ADP-ribose) polymerase (PARP) inhibitors, and radioligand treatment. The existing guidelines only provide a few treatment recommendations for older patients; however, the treatment of older patients should primarily consider not only chronological age but also the patient's psychological and physical condition and preferences. In this context, the geriatric assessment represents an important instrument for determining the treatment strategy., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Skin-sparing (SSME) and nipple-sparing mastectomy (NSME) were developed to improve the cosmetic results for breast cancer (BC) patients, both allowing for immediate breast reconstruction. Recommendations for post-mastectomy radiotherapy (PMRT) are primarily derived from trials where patients were treated by standard mastectomies. Due to their more conservative character, SSME and especially NSME potentially leave more glandular tissue at risk for subclinical disease., Methods: Rates and sites of locoregional failures following SSME and NSME plus/minus reconstruction were analyzed regarding tumor stage and biological risk factors. In particular, the role of PMRT in "intermediate"-risk and early stage high-risk breast cancer patients was revisited. Implications on targeting and dose delivery of PMRT were critically reviewed., Results: The value of PMRT in stage III BC remains undisputed. For node-negative BC patients, the majority of reports classify clinical and biological features such as tumor size, close surgical margins, premenopausal status, multicentricity, lymphangiosis, triple-negativity, HER2-overexpression, and poor tumor grading as associated with higher rates of locoregional relapse, thus, building an "intermediate" risk group. Surveys revealed that the majority of radiation oncologists use risk-adaptive models also considering the number of coinciding factors for the estimation of recurrence probability following SSME and NSME. Constellations with a 10-year locoregional recurrence risk of >10% are usually triggering the indication for PMRT. There was no common belief that the amount of residual tissue, e.g., tissue thickness over flaps, serves as additional decision aid. Modern treatment planning can ensure optimal dose distribution for PMRT in almost all patients with SSME. There are no reliable data supporting a reduction of the treatment volume from the CTV chest wall, e.g., to the nipple-areola complex, to the dorsal aspect behind the implant volume, the pectoralis muscle, nor the regional interpectoral, axillary, or complete regional lymph nodes only. The omission of a skin bolus in intermediate-risk BC does not compromise oncological safety., Conclusions: For intermediate-risk as well as early stage high-risk BC patients, the DEGRO Breast Cancer Expert Panel recommends the use of PMRT following SSME and NSME when a 10-year locoregional recurrence risk is likely to be greater than 10%, as estimated by clinical and biological risk factors. Subvolume-only radiation is discouraged outside of trials. The impact of adequate systemic treatment and the value of radiotherapy on optimal locoregional tumor control, with the goal of less than 5% LRR at 10-years follow-up, has to be verified in prospective trials.

Monitoring of radiochemotherapy (RCX) in patients with glioblastoma is difficult because unspecific alterations in magnetic resonance imaging with contrast enhancement can mimic tumor progression. Changes in tumor to brain ratios (TBRs) in positron emission tomography (PET) using O-(2-¹⁸fluoroethyl)-l-tyrosine (¹⁸F-FET) after RCX with temozolomide of patients with glioblastoma have been shown to be valuable parameters to predict survival. The kinetic behavior of ¹⁸F-FET in the tumors is another promising parameter to analyze tumor metabolism. In this study, we investigated the predictive value of dynamic ¹⁸F-FET PET during RCX of glioblastoma. Time-activity curves (TACs) of ¹⁸F-FET uptake of 25 patients with glioblastoma were evaluated after surgery (FET-1), early (7-10 days) after completion of RCX (FET-2), and 6 to 8 weeks later (FET-3). Changes in the time to peak (TTP) and the slope of the TAC (10-50 minutes postinjection) were analyzed and related to survival. Changes in kinetic parameters of ¹⁸F-FET uptake after RCX showed no relationship with survival time. In contrast, the high predictive value of changes of TBR to predict survival was confirmed. We conclude that dynamic ¹⁸F-FET PET does not provide additional prognostic information during RCX. Static ¹⁸F-FET PET imaging (20-40 minutes postinjection) appears to be sufficient for this purpose and reduces costs.

Background and Purpose: The aim of the study was to evaluate the impact of a dose escalation to an (18)F-choline PET-CT defined simultaneous integrated boost (IB) on the dose distribution and changes of the equivalent uniform dose (EUD)., Materials and Methods: PET-CT was performed in 12 consecutive patients for treatment planning. An intraprostatic lesion was defined by a tumour-to-background uptake value ratio >2 (GTV(PET)). Dose escalation was focused only on the intraprostatic lesion. Two comparisons were evaluated: whole prostate irradiation to 76 Gy+/-boost to 80 Gy (C1) and whole prostate irradiation to 66.6 Gy+/-boost to 83.25 Gy (C2)., Results: PTV/GTV(PET)+margins were covered by a mean EUD of 75.9/76.1 Gy vs. 77.1/80.1 Gy (C1) and 66.5/66.2 Gy vs. 71.1/82.9 Gy (C2) (p<0.01, respectively). Concerning the organs at risk, EUD increased slightly with an additional boost (mean EUD for bladder: C1 53.2 Gy vs. 53.8 Gy; C2 43.0 Gy vs. 45.1 Gy; for rectum: C1 52.0 Gy vs. 52.6 Gy; C2 43.0 Gy vs. 45.4 Gy; p<0.01, respectively). The distance to the organs at risk had a significant impact on the respective maximum doses in the treatment plans with IB., Conclusions: Treatment planning with IB allows an individually adapted dose escalation. The therapeutic ratio can be improved by a considerable dose escalation to the macroscopic tumour, but only minor EUD changes to the bladder and rectum.

Background and Purpose: The aim of the study was to compare quality of life after permanent I-125 brachytherapy (BT) and external beam radiotherapy (EBRT) for prostate cancer., Materials and Methods: A group of 104 patients (52 in each group) have been surveyed prospectively before EBRT/BT (time A), at the last day of EBRT (70.2-72.0 Gy) or one month after BT (time B), and a median time of 16 months after EBRT/BT (time C) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Pairs were matched according to the following criteria: age +/-5 years, prostate volume +/-10 cc, use of antiandrogens, and erectile function., Results: Urinary function/bother scores decreased significantly more after BT both at time B and time C. Bowel function/bother scores tended to be higher after BT, with a lower percentage of patients with painful bowel movements (BT: 12%/27%/15%; EBRT: 19%/52%/35% at time A/B/C; p<0.05 for differences at times B/C) and rectal bleeding (BT: 12%/12%/12%; EBRT: 8%/14%/17%). No difference concerning erectile dysfunction was found (67% vs. 61% with preserved erections firm enough for intercourse after BT vs. EBRT at time C)., Conclusions: BT was associated with higher urinary, but lower rectal toxicity. The risk of treatment-associated erectile dysfunction did not differ between these methods.

Background: There is a lack of prospective studies focusing on the sexual quality of life of prostate cancer patients after conformal radiotherapy (RT)., Objective: To evaluate the incidence, progression, and predictive factors for erectile dysfunction (ED)., Design, Setting and Participants: Patients who responded to the sexual domain of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire before and more than 1 yr after RT and never received an antiandrogen treatment were included (n=123)., Intervention: RT dose was 70.2-72 Gy. Eleven patients used a phosphodiesterase-5 (PDE-5) inhibitor., Measurements: Patients responded to the EPIC questionnaire before (time A), at the last day (B), a median time of 2 mo after (C), and 16 mo after (D) RT. In a multivariate analysis, risk factors (patient age, prostate volume, planning target volume, use of PDE-5 inhibitor, comorbidities) were tested for their independent effects on ED before and after RT., Results and Limitations: Sexual function and bother scores had already decreased by the end of RT (median function and bother scores at times A/B/C/D: 41/30/32/24 and 75/50/50/50). Initial function scores correlated well with late function scores (r=0.7; p<0.001). The ability to have an erection was reported by 81%/72%/74%/60% (preserved erectile ability in 70% at time D), erections firm enough for sexual intercourse by 44%/33%/35%/27% (preserved erections sufficient for intercourse in 53% at time D) of patients. A higher patient age and diabetes were predictive of both a pre-existing ED and a post-RT acquired ED. Nightly erections before treatment proved prognostically favourable (at least weekly vs. < weekly-hazard ratio of 5.9 for preserved erections sufficient for intercourse; p=0.01). Higher rates of ED can be expected with longer follow-up., Conclusions: The incidence of ED progressively increases after RT. Patient age and diabetes are risk factors for both pre-treatment and RT-associated ED. Nightly erections before RT proved prognostically favourable.

Background: Rectal cancer is a common malignant disease and occurs not infrequently in younger men. We verified the dose to the testes from scattered radiation in adjuvant pelvic irradiation following anterior resection of rectal cancer., Patients and Method: We measured the scattered gonadal dose of 18 patients in vivo with thermoluminescence detectors, which were fixed on four defined points on the scrotum during radiation on three consecutive days. All patients were treated three-dimensionally planned using a three-field box lying in prone position in a bellyboard. A total dose of 50.4 Gy was given in 28 fractions of 1.8 Gy. From 45 up to 50.4 Gy the radiation fields were modified to lateral-opposing fields which were shortened from the top to protect the small bowel., Results: The mean gonadal dose per fraction of all patients was 0.057 Gy (median 0.05 Gy) with a range between 0.035 and 0.114 Gy. The standard deviation was 0.02 Gy. The calculated cumulative mean gonadal dose after 28 fractions was 1.60 Gy (0.98-3.19 Gy)., Conclusions: Germinal epithelium is very sensitive to low-dose irradiation, according to a negative fractionation effect. It is known that gonadal total doses of 1 Gy with single doses of 0.03-0.05 Gy can result in a temporary azoospermia with following recovery in most cases. If gonadal total doses exceed 1.5 Gy a substantial increase in irreversible azoospermia must be expected. With respect to the data reported in the literature our measured mean gonadal total dose of 1.60 Gy will lead with high probability to an irreversible infertility. Because of the small number of patients in our study, the data must be interpreted with caution, however, it is very important in patient's informed consent to draw attention to the high risk of infertility. The possibility of sperm cryoconservation should be discussed with the patient.