The tumor core boost study: A feasibility study of radical dose escalation to the central part of large tumors with an integrated boost in the palliative treatment setting.

PURPOSE: For patients with large tumors palliative radiotherapy often is the only local treatment option. To prevent toxicity the administered doses are low. Dose escalation to the tumor could be an option to better smyptom control and prolong local control rates. In this prospective study we used a very pragmatic approach with a simultaneously integrated boost (SIB) to an almost geometrically defined tumor core to achieve this. The primary endpoint was to demonstrate feasibility. METHOD: Patients with solid tumors > 4 cm in diameter of different histologies were eligible in this single arm, prospective, multi-institutional clinical feasibility trial with two treatment concepts: 5â€¯× 5 Gy with an integrated boost to the tumor core of 5â€¯× 10 Gy or 10â€¯× 3 Gy with a boost of 10â€¯× 6 Gy. The objective of dose escalation in this study was to deliver a minimum dose of 150% of the prescribed dose to the gross tumor volume (GTV) tumor core and to reach a maximum of at least 200% in the tumor core. RESULTS: In all, 21 patients at three study sites were recruited between January 2019 and November 2020 and were almost evenly spread (9 to 12) between the two concepts. The treated planning target volumes (PTV) averaged 389.42 cm3 (range 49.4-1179.6 cm3). The corresponding core volumes were 72.85 cm3 on average (range 4.21-338.3 cm3). Dose escalation to the tumor core with mean doses of 167.7-207.7% related to the nonboost prescribed isodose led to PTV mean doses of 120.5-163.3%. Treatment delivery and short-term follow-up was successful in all patients. CONCLUSIONS: Palliative radiotherapy with SIB to the tumor core seems to be a feasible and well-tolerated treatment concept for large tumors. The applied high doses of up to 50 Gy in 5 fractions (or 60 Gy in 10 fractions) did not cause unexpected side effects in the 42 day follow-up period. Further research is needed for more information on efficacy and long-term toxicity.

Reduction of immunosuppression combined with whole-brain radiotherapy and concurrent systemic rituximab is an effective yet toxic treatment of primary central nervous system post-transplant lymphoproliferative disorder (pCNS-PTLD): 14 cases from the prospective German PTLD registry.

Post-transplant lymphoproliferative disorders (PTLD) exclusively affecting the central nervous system-primary CNS-PTLD (pCNS-PTLD)-are rare. There is no standard therapy, and previous case series have included heterogeneous treatment approaches. We performed a retrospective, multi-centre analysis of 14 patients with pCNS-PTLD after solid organ transplantation (SOT) treated in the prospective German PTLD registry with reduction of immunosuppression (RI), whole-brain radiotherapy (WBRT), and concurrent systemic rituximab between 2001 and 2018. Twelve of fourteen patients were kidney transplant recipients and median age at diagnosis was 65 years. Thirteen of fourteen cases (93%) were monomorphic PTLD of the diffuse large B-cell lymphoma type, and 12/13 were EBV-associated. The median dose of WBRT administered was 40 Gy with a median fraction of 2 Gy. The median number of administered doses of rituximab (375 mg/m2) IV was four. All ten patients evaluated responded to treatment (100%). Median OS was 2.5 years with a 2-year Kaplan-Meier estimate of 63% (95% confidence interval 30-83%) without any recorded relapses after a median follow-up of 2.6 years. Seven of fourteen patients (50%) suffered grade III/IV infections under therapy (fatal in two cases, 14%). During follow-up, imaging demonstrated grey matter changes interpreted as radiation toxicity in 7/10 evaluated patients (70%). The combination of RI, WBRT, and rituximab was an effective yet toxic treatment of pCNS-PTLD in this series of 14 patients. Future treatment approaches in pCNS-PTLD should take into account the significant risk of infections as well as radiation-induced neurotoxicity.

Low-dose external beam radiotherapy for greater trochanteric pain syndrome : Target volume definition and treatment outcome.

PURPOSE: Low-dose external beam radiotherapy (ED-EBRT) is frequently used in the therapy of refractory greater trochanteric pain syndrome (GTPS). As studies reporting treatment results are scarce, we retrospectively analyzed our own patient collectives. PATIENTS AND METHODS: In all, 60 patients (74 hips) received LD-EBRT (6 × 0.5 Gy in 29 hips, 6 × 1 Gy in 45). The endpoint was the patient's reported subjective response to treatment. The influence of different patient and treatment characteristics on treatment outcome was investigated. RESULTS: At the end of LD-EBRT, 69% reported partial remission, 4% complete remission, no change 28%. A total of 3 months later (n = 52 hips), the results were 37, 33, and 30% and 18 months after LD-EBRT (n = 47) 21, 51, and 28%. In univariate analysis "inclusion of the total femoral head into the PTV" and "night pain before LD-EBRT" were correlated with symptom remission at the end of LD-EBRT, while "initial increase in pain during LD-EBRT" was significantly associated with treatment failure. In multivariable modeling "initial increase in pain" was identified as a risk factor for treatment failure (p = 0.007; odds ratio [OR] 0.209; 95% confidence interval [CI] 0.048-0.957), while "night pain" was an independent factor for remission (p = 0.038; OR 3.484; 95% CI 1.004-12.6). Three months after LD-EBRT "night pain" and "inclusion of the complete femoral neck circumference into the PTV" were predictive for remission. CONCLUSION: LD-EBRT represents a useful treatment option for patients suffering from GTPS. Three months after therapy two-thirds of the patients reported a partial or complete symptom remission. Especially patients who suffered from nocturnal pain seemed to benefit. Treatment appeared to be more effective when the entire circumference of the femoral neck was encompassed.

The field size matters: low dose external beam radiotherapy for thumb carpometacarpal osteoarthritis : Importance of field size.

The purpose of this work was to evaluate the efficacy of low-dose radiotherapy (RT) for thumb carpometacarpal osteoarthritis (rhizarthrosis). The responses of 84 patients (n = 101 joints) were analyzed 3 months after therapy (n = 65) and at 12 months (n = 27). Patients were treated with 6 fractions of 1 Gy, two times a week, with a linear accelerator. At the end of therapy, about 70 % of patients reported a response (partial remission or complete remission), 3 months later about 60 %, and 1 year after treatment 70 %. In univariate regression analysis, higher patient age and field size greater than 6 × 4 cm were associated with response to treatment, while initial increase of pain under treatment was predictive for treatment failure. Duration of RT series (more than 18 days), gender, time of symptoms before RT, stress pain or rest pain, or prior ortheses use, injections, or surgery of the joint were not associated with treatment efficacy. In multivariate regression analysis, only field size and initial pain increase were highly correlated with treatment outcome. In conclusion, RT represents a useful treatment option for patients suffering from carpometacarpal osteoarthritis. In contrast to other benign indications, a larger field size (>6 × 4 cm) seems to be more effective than smaller fields and should be evaluated in further prospective studies.

Tangential vs. defined radiotherapy in early breast cancer treatment without axillary lymph node dissection: a comparative study.

PURPOSE: Recent studies have demonstrated low regional recurrence rates in early-stage breast cancer omitting axillary lymph node dissection (ALND) in patients who have positive nodes in sentinel lymph node dissection (SLND). This finding has triggered an active discussion about the effect of radiotherapy within this approach. The purpose of this study was to analyze the dose distribution in the axilla in standard tangential radiotherapy (SRT) for breast cancer and the effects on normal tissue exposure when anatomic level I-III axillary lymph node areas are included in the tangential radiotherapy field configuration. PATIENTS AND METHODS: We prospectively analyzed the dosimetric treatment plans from 51 consecutive women with early-stage breast cancer undergoing radiotherapy. We compared and analyzed the SRT and the defined radiotherapy (DRT) methods for each patient. The clinical target volume (CTV) of SRT included the breast tissue without specific contouring of lymph node areas, whereas the CTV of DRT included the level I-III lymph node areas. RESULTS: We evaluated the dose given in SRT covering the axillary lymph node areas of level I-III as contoured in DRT. The mean VD95% of the entire level I-III lymph node area in SRT was 50.28% (range, 37.31-63.24%), VD45 Gy was 70.1% (54.8-85.4%), and VD40 Gy was 83.5% (72.3-94.8%). A significant difference was observed between lung dose and heart toxicity in SRT vs. DRT. The V20 Gy and V30 Gy of the right and the left lung in DRT were significantly higher in DRT than in SRT (p<0.001). The mean heart dose in SRT was significantly lower (3.93 vs. 4.72 Gy, p=0.005). CONCLUSION: We demonstrated a relevant dose exposure of the axilla in SRT that should substantially reduce local recurrences. Furthermore, we demonstrated a significant increase in lung and heart exposure when including the axillary lymph nodes regions in the tangential radiotherapy field set-up.

The impact of palliative radiotherapy on health-related quality of life in patients with head and neck cancer - Results of a multicenter prospective cohort study.

Purpose: Palliative radiotherapy for patients with head and neck cancer can be used to alleviate symptoms. Only a few studies have investigated its impact on patient-reported outcomes (PRO). Therefore, we conducted a prospective multicenter observational study. The primary objective was to assess changes in health-related quality of life (HrQoL) per PRO. Methods: Eligibility criteria included i.) head and neck cancer and ii.) palliative radiotherapy indicated (EQD2Gy < 60 Gy). The primary follow-up date was eight weeks after radiotherapy (t8w). PRO measures included the EORTC QLQ-C30 and EORTC QLQ-H&N43 and pain per Numeric Rating Scale (NRS). Per protocol, five PRO domains were to be reported in detail as well as PRO domains corresponding to a primary and secondary symptom as determined by the individual patient. We defined a minimal important difference (MID) of 10 points. Results: From 06/2020 to 06/2022, 61 patients were screened and 21 patients were included. Due to death or decline in health-status, HrQoL data was available for 18 patients at the first fraction and for eight patients at t8w. The MID was not met for the predefined domains in terms of mean values as compared from first fraction to t8w. Individually in those patients with available HrQoL data at t8w, 71% (5/7) improved in their primary and 40% (2/5) in their secondary symptom domain reaching the MID from first fraction to t8w, respectively. There was a significant improvement in pain per NRS in those patients with available data at t8w per Wilcoxon signed rank test (p = 0.041). Acute mucositis of grade ≥3 per CTCAE v5.0 occurred in 44% (8/18) of the patients. The median overall survival was 11 months. Conclusion: Despite low patient numbers and risk of selection bias, our study shows some evidence of a benefit from palliative radiotherapy for head and neck cancer as measured by PRO.German Clinical Trial Registry identifier: DRKS00021197.

Radiotherapy of Breast Cancer in Laterally Tilted Prone vs. Supine Position: What about the Internal Mammary Chain?

BACKGROUND: In the multimodal breast-conserving curative therapy of some high-risk breast cancer patients, extended external beam radiotherapy (EBRT) not only to the breast but also to the supraclavicular fossa and the internal mammary chain (parasternal region (PSR)) is indicated. We report a dosimetric study on the EBRT of the breast ("B") and the breast including PSR ("B + PSR"), comparing the supine and the laterally tilted prone patient positions in free breathing. METHODS: The planning CT scans of 20 left- and 20 right-sided patients were analyzed. EBRT plans were calculated with 3D conformal EBRT (3D) and with intensity-modulated EBRT (IMRT) for "B" and "B + PSR" in the prone and supine positions. The mean and threshold doses were computed. The quality of EBRT plans was compared with an overall plan assessment factor (OPAF), comprising three subfactors, homogeneity, conformity, and radiogenic exposure of OAR. RESULTS: In the EBRT of "B", prone positioning significantly reduced the exposure of the OARs "heart" and "ipsilateral lung" and "lymphatic regions". The OPAF was significantly better in the prone position, regardless of the planning technique or the treated breast side. In the EBRT of "B + PSR", supine positioning significantly reduced the OAR "heart" exposure but increased the dose to the OARs "ipsilateral lung" and "lymphatic regions". There were no significant differences for the OPAF, independent of the irradiated breast side. Only the IMRT planning technique increased the chance of a comparatively good EBRT plan. CONCLUSION: Free breathing prone positioning significantly improves plan quality in the EBRT of the breast but not in the EBRT of the breast + PSR.

Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions.

Microglia are crucially important myeloid cells in the CNS and constitute the first immunological barrier against pathogens and environmental insults. The factors controlling microglia recruitment from the blood remain elusive and the direct circulating microglia precursor has not yet been identified in vivo. Using a panel of bone marrow chimeric and adoptive transfer experiments, we found that circulating Ly-6C(hi)CCR2(+) monocytes were preferentially recruited to the lesioned brain and differentiated into microglia. Notably, microglia engraftment in CNS pathologies, which are not associated with overt blood-brain barrier disruption, required previous conditioning of brain (for example, by direct tissue irradiation). Our results identify Ly-6C(hi)CCR2(+) monocytes as direct precursors of microglia in the adult brain and establish the importance of local factors in the adult CNS for microglia engraftment.

Prospective Evaluation of Low-Dose External Beam Radiotherapy (LD-EBRT) for Painful Trapeziometacarpal Osteoarthritis (Rhizarthrosis) on Pain, Function, and Quality of Life to Calculate the Required Number of Patients for a Prospective Randomized Study.

Background: Retrospective studies have described the effectiveness of low-dose radiotherapy (LD-EBRT) in painful arthrosis of small finger joints, but two recent prospective studies have yielded ambiguous results. To generate accurate data for the planning of a trial, we conducted a prospective, monocentric, observational study to describe the effects of LD-EBRT as precisely as possible. Methods: Twenty-five consecutive patients with symptomatic trapeziometacarpal (TMC) arthrosis were irradiated with 6 × 0.5 Gy. Before, 3, and 12 months after LD-EBRT, we assessed subjective endpoints (modified "von-Pannewitz score", 10-point visual analogue scale (VAS), "patient-rated wrist evaluation" (PRWE)), and objective measurements ("active range of motion" (AROM), Kapandji index, grip strength, pinch grip). Results: At 3/12 months, 80%/57% reported partial and 4%/18% complete remission according to the "von-Pannewitz" score. VAS "overall pain" significantly decreased from a median of seven (IQR 4) at baseline to three (IQR 6; p = 0.046) and to two (IQR 2; p = 0.013). Similar results were obtained for VAS "pain during exercise", VAS "pain during daytime", and VAS "function". "PRWE overall score" was reduced from 0.5 at baseline (SD 0.19) to 0.36 (SD 0.24, p = 0.05) and to 0.27 (SD 0.18, p = 0.0009). We found no improvements of the objective endpoints (AROM, Kapandji, grip strength) except for flexion, which increased from 64° (SD 12°) at baseline to 73° (SD 9.7°, p = 0.046) at 12 months. Conclusions: We recommend the PRWE score as a useful endpoint for further studies for this indication. To prove a 15% superiority over sham irradiation, we calculated that 750 patients need to be prospectively randomized.

Combined wIRA-Hyperthermia and Hypofractionated Re-Irradiation in the Treatment of Locally Recurrent Breast Cancer: Evaluation of Therapeutic Outcome Based on a Novel Size Classification.

Effective tumor control in patients suffering from unresectable locally recurrent breast cancer (LRBC) in pre-irradiated areas can be achieved by re-irradiation combined with superficial hyperthermia. Using this combined modality, total re-irradiation dose and toxicity can be significantly reduced compared to conventionally fractionated treatment schedules with total doses of 60-66 Gy. Applying contact-free, thermography-controlled water-filtered infrared-A superficial hyperthermia, immediately followed by hypofractionated re-irradiation, consisting of 4 Gy once per week up to a total dose of 20 Gy, resulted in high overall response rates even in large-sized tumors. Comparability of clinical data between different combined Hyperthermia (HT)/Radiotherapy (RT) treatment schedules is impeded by the highly individual characteristics of this disease. Tumor size, ranging from microscopic disease and small lesions to large-sized cancer en cuirasse, is described as one of the most important prognostic factors. However, in clinical studies and analyses of LRBC, tumor size has so far been reported in a very heterogeneous way. Therefore, we suggest a novel, simple and feasible size classification (rClasses 0-IV). Applying this classification for the evaluation of 201 patients with pre-irradiated LRBC allowed for a stratification into distinct prognostic groups.

Patient-Reported Outcomes-Secondary Analysis of the SCORE-2 Trial Comparing 4 Gy × 5 to 3 Gy × 10 for Metastatic Epidural Spinal Cord Compression.

PURPOSE: To compare 4 Gy × 5 (1 week) to 3 Gy × 10 (2 weeks) in relieving pain and distress in patients with metastatic epidural spinal cord compression (MESCC). METHODS AND MATERIALS: The randomized SCORE-2 trial compared 4 Gy × 5 (n = 101) to 3 Gy × 10 (n = 102) for MESCC. In this additional analysis, these regimens were compared for their effect in relieving pain and distress. Distress was evaluated with the distress-thermometer (0 = no distress, 10 = extreme distress) and pain on a linear scale (0 = no pain, 10 = worst pain). Relief of distress was defined as decrease of ≥2 points; complete and partial pain relief were defined as achieving a score of 0 points and a decrease ≥2 points, respectively, without increase of analgesic use. This prospective secondary analysis of the SCORE-2 trial aimed to show that 4 Gy × 5 was not inferior to 3 Gy × 10 regarding distress and pain relief. Analyses were performed using the unconditional test of noninferiority for binomial differences based on restricted maximum likelihood estimates (noninferiority margin: -20%). Evaluations were performed before, directly after, and 1, 3, and 6 months after radiation therapy. (ClinicalTrials.gov: NCT02189473). RESULTS: At baseline, median distress scores were 8 (2-10) points in the 4 Gy × 5 group and 8 (2-10) points in the 3 Gy × 10 group. At 1 month, distress relief rates were 58.1% (43/74) and 62.7% (47/75) (difference: -4.6%; 95% confidence interval, -20.0% to +11.1%; P = .025). At baseline, median pain scores were 7 (2-10) and 7 (2-10) points, respectively. At 1 month, complete pain relief rates were 23.5% (16/68) versus 20.0% (14/70) (difference, +3.5%; 95% confidence interval, -10.4% to +17.5%; P < .001), and overall pain relief rates were 52.9% (36/68) versus 57.1% (40/70) (difference, -4.2%; 95% confidence interval, -20.5% to +12.3%; P = .029). Distress and pain relief rates after 4 Gy × 5 were largely comparable to 3 Gy × 10 at all time points. Associated 95% confidence intervals did not point toward any relevant differences. CONCLUSIONS: In patients with MESCC and poor to intermediate survival prognoses, 4 Gy × 5 appeared noninferior to 3 Gy × 10 regarding pain and distress relief.

Thymic alterations in mice deficient for the SNARE protein VAMP8/endobrevin.

SNARE (soluble-N-ethylmaleimide-sensitive factor attachment receptor) proteins mediate the recognition and fusion of transport vesicles in eukaryotic cells. The SNARE protein VAMP8 (also called endobrevin) is involved in the fusion of late endosomes and in some pathways of regulated exocytosis. In a subset of mice deficient for the SNARE protein VAMP8, a severe alteration of the thymus and in T lymphocyte development was observed and characterized. The size of the thymus and the number of thymocytes were dramatically reduced compared with those in heterozygous littermates. Further, the compartmentalization into cortex and medulla and the organization of the thymus epithelium were disturbed. The numbers of all thymocyte subpopulations were reduced, with the CD4 and CD8 double-positive thymocytes being most severely affected. The proportion of proliferating thymocytes was reduced, and the staining of apoptotic cells in situ and ex vivo indicated an increased number of apoptotic cells. Isolated thymocytes of Vamp8 (-/-) mice were more susceptible to various apoptotic stimuli including glucocorticoids, FAS receptor, and CD3/CD28-mediated signaling in vitro, even before an increased number of apoptotic cells was detectable in situ. However, bone marrow of phenotypically affected Vamp8 (-/-) mice was readily able to repopulate immunodeficient hosts suggesting that the SNARE protein VAMP8 has a specific function in the thymic stroma affecting the proliferation and apoptosis of T lymphocytes during maturation in the thymus.

The combined effect of fludarabine monophosphate and radiation as well as gemcitabine and radiation on squamous carcinoma tumor cell lines in vitro.

PURPOSE: Despite proven antitumor activity of gemcitabine in chemoradiotherapy of advanced head and neck cancer, many authors refer to severe acute and late local and haematological toxicity. Fludarabine does imply nearly the same mechanisms of action as gemcitabine, inhibiting various enzymes involved in DNA replication. This investigation focuses on the combined effect of either fludarabine or gemcitabine and radiation on human squamous carcinoma cell lines in vitro, providing data for future decisions on head and neck chemoradiotherapy regimen. MATERIALS AND METHODS: ZMK-1, A549, BW-225, GR-145, OH-65 and CaSki cell lines were incubated with either drug at defined schedules and irradiated at a single fraction dose of 2 Gy every 24 hours up to 8 Gy. Cytotoxic effects were measured by colony-forming assays, quantitative determination of apoptosis and isobologram analysis. RESULTS: Incubation of fludarabine led to a radiosensitizing effect in the A549, CaSki and ZMK-1 cell lines and an additive effect in the BW-225, GR-145 and OH-65 cell lines. Treatment with gemcitabine only indicated significant radiosensitization in the CaSki cell line in combination with augmented resistance against gemcitabine application alone. CONCLUSIONS: Our results reveal a potential radiosensitizing effect of fludarabine and its possible application in chemoradiotherapy of advanced head and neck carcinoma and possibly other tumor entities.

Plasminogen activator inhibitor-1 from bone marrow-derived cells suppresses neointimal formation after vascular injury in mice.

OBJECTIVE: To investigate the ability of bone marrow (BM)-derived cells to modulate neointimal growth after injury by expressing plasminogen activator inhibitor-1 (PAI-1). METHODS AND RESULTS: We performed BM transplantation (BMT) in lethally irradiated wild-type (WT) and PAI-1(-/-) mice. Three weeks after carotid injury with ferric chloride, analysis of Y-chromosome DNA expression in the vessel wall of female hosts revealed that 20.8+/-6.0% of the cells in the neointima and 37.6+/-5.7% of those in the media were of BM origin. Lack of PAI-1 in either the host or the donor cells did not affect recruitment of BM-derived cells into sites of vascular injury. The neointima consisted predominantly of smooth muscle cells, and a proportion of these cells expressed PAI-1. Overall, lack of PAI-1 was associated with enhanced neointimal formation. However, importantly, BMT(WT-->PAI-1(-/-)) mice exhibited reduced neointimal area (P=0.05) and luminal stenosis (P=0.04) compared with BMT(PAI-1(-/-)-->PAI-1(-/-)) mice. Although PAI-1-expressing cells were shown to be present in BMT(WT-->PAI-1(-/-)) lesions, these mice did not exhibit detectable levels of the inhibitor in the circulation, suggesting that local production of PAI-1 by cells in the neointima and media was sufficient to reduce luminal stenosis. CONCLUSIONS: PAI-1 from BM-derived cells appears capable of suppressing neointimal growth after vascular injury.

Galectin-1 expression in human glioma cells: modulation by ionizing radiation and effects on tumor cell proliferation and migration.

Galectins are evolutionarily conserved beta-galactoside-binding lectins which recognize specific glycoconjugates on the cell surface and the extracellular matrix. Accumulating evidence indicates that these proteins are involved in a variety of physiological and pathological processes including tumor growth and metastasis. Up-regulated expression of galectin-1 is a hallmark of a variety of malignant tumors. Here, we examined the expression of galectin-1 in glioma cell lines, the influence of ionizing irradiation and the intracellular and extracellular effects of this protein on tumor cell proliferation and migration. Galectin-1 was detected in both A172 and U118 glioma cells by immunoblot analysis. Ionizing irradiation induced a statistically significant up-regulation in glioma cell lines. RNA-interference-mediated silencing resulted in a significant suppression of the proliferation of the A172 cells, while the addition of recombinant galectin-1 had no effect. On the other hand, the migratory capacity of both cell lines was reduced after galectin-1 down-regulation, and up-regulated by the addition of exogenous galectin-1. Our results provide evidence of a role for galectin-1 in the regulation of glioma cell proliferation and migration. While an intracellular mechanism seemed to prevail in galectin-1-mediated regulation of tumor cell proliferation, the control of cell migration was exerted by both intracellular and extracellular mechanisms. In addition, this protein was up-regulated by ionizing radiation, indicating that the blockade of this protein should be performed before radiotherapy to avoid any undesired stimulating effects. Given the multifactorial role of galectin-1 in the regulation of tumor escape and metastasis, we conclude that targeting galectin-1 may have therapeutic benefits in the treatment of malignant glioma.

Comparison of different contouring definitions of the rectum as organ at risk (OAR) and dose-volume parameters predicting rectal inflammation in radiotherapy of prostate cancer: which definition to use?

OBJECTIVE: The objective of this retrospective planning study was to find a contouring definition for the rectum as an organ at risk (OAR) in curative three-dimensional external beam radiotherapy (EBRT) for prostate cancer (PCa) with a predictive correlation between the dose-volume histogram (DVH) and rectal toxicity. METHODS: In a pre-study, the planning CT scans of 23 patients with PCa receiving definitive EBRT were analyzed. The rectum was contoured according to 13 different definitions, and the dose distribution was correlated with the respective rectal volumes by generating DVH curves. Three definitions were identified to represent the most distinct differences in the shapes of the DVH curves: one anatomical definition recommended by the Radiation Therapy Oncology Group (RTOG) and two functional definitions based on the target volume. In the main study, the correlation between different relative DVH parameters derived from these three contouring definitions and the occurrence of rectal toxicity during and after EBRT was studied in two consecutive collectives. The first cohort consisted of 97 patients receiving primary curative EBRT and the second cohort consisted of 66 patients treated for biochemical recurrence after prostatectomy. Rectal toxicity was investigated by clinical investigation and scored according to the Common Terminology Criteria for Adverse Events. Candidate parameters were the volume of the rectum, mean dose, maximal dose, volume receiving at least 60 Gy (V60), area under the DVH curve up to 25 Gy and area under the DVH curve up to 75 Gy in dependence of each chosen rectum definition. Multivariable logistic regression considered other clinical factors such as pelvine lymphatics vs local target volume, diabetes, prior rectal surgery, anticoagulation or haemorrhoids too. RESULTS: In Cohort 1 (primary EBRT), the mean rectal volumes for definitions "RTOG", planning target volume "(PTV)-based" and "PTV-linked" were 100 cm3 [standard deviation (SD) 43 cm3], 60 cm3 (SD 26 cm3) and 74 cm3 (SD 31 cm3), respectively (p < 0.01; analysis of variance). The mean rectal doses according to these definitions were 35 Gy (SD 8 Gy), 48 Gy (SD 4 Gy) and 44 Gy (SD 5 Gy) (p < 0.01). In Cohort 2 (salvage EBRT), the mean rectal volumes were 114 cm3 (SD 47 cm3), 64 cm3 (SD 26 cm3) and 81 cm3 (SD 30 cm3) (p < 0.01) and the mean doses received by the rectum were 36 Gy (SD 8 Gy), 49 Gy (SD 5 Gy) and 44 Gy (SD 5 Gy) (p < 0.01). Acute or subacute rectal inflammation occurred in 69 (71.9%) patients in Cohort 1 and in 43 (70.5%) in Cohort 2. We did not find a correlation between all investigated DVH parameters and rectal toxicity, irrespective of the investigated definition. By adding additional variables in multivariate analysis, the predictive ability was substantially improved. Still, there was essentially no difference in the probability of predicting rectal inflammation occurrence between the tested contouring definitions. CONCLUSION: The RTOG anatomy-based recommendations are questionable in comparison with functional definitions, as they result in higher variances in several relative DVH parameters. Moreover, the anatomy-based definition is no better and no worse in the predictive value concerning clinical end points. Advances in knowledge: Functional definitions for the rectum as OAR are easier to apply, faster to contour, have smaller variances and do not offer less information than the anatomy-based RTOG definition.

Long-term follow-up after transoral laser microsurgery and adjuvant radiotherapy for advanced recurrent squamous cell carcinoma of the head and neck.

PURPOSE: The aim of this study was to evaluate the efficacy of adjuvant radiotherapy after transoral laser microsurgery for advanced recurrent head-and-neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Between 1988 and 2000, 37 patients with advanced local recurrences (23 local and 14 locoregional recurrences) of HNSCC without distant metastases were treated in curative intent with organ-preserving transoral laser microsurgery and adjuvant radiotherapy (before 1994 split-course radiotherapy with carboplatinum, after 1994 conventional radiotherapy). Initial therapy of the primary (8.1% oral cavity, 35.1% oropharynx, 13.5% hypopharynx, and 43.3% larynx) before relapse was organ-preserving transoral laser microsurgery without any adjuvant therapy. RESULTS: After a median follow-up of 124 months, the 5-year overall survival rate was 21.3%, the loco-regional control rate 48.3%, respectively. In multivariate analysis, stage of original primary tumor (Stage I/II vs. Stage III/IV), and patient age (<58 years vs. >or=58 years) showed statistically significant impact on prognosis. In laryngeal cancer, larynx preservation rate after treatment for recurrent tumor was 50% during follow-up. CONCLUSION: Our data show that organ-preserving transoral laser microsurgery followed by adjuvant radiotherapy is a curative option for patients who have advanced recurrence after transoral laser surgery and is an alternative to radical treatment.

Prostate-Specific Membrane Antigen PET/CT: False-Positive Results due to Sarcoidosis?

We report on a 72-year-old male patient who developed sarcoidosis of the mediastinal lymph nodes, the liver, and the prostate 11 years ago. Seven years later, he underwent transurethral resection of the prostate by laser due to hematuria. Pathology of the resected chips showed a 'granulomatous prostatitis with epitheloid cells'. Malignancy was histologically excluded at that time. Four years later, he was diagnosed with an undifferentiated prostate carcinoma, with a Gleason score of 5 + 4 = 9. After initiation of antihormonal therapy, he underwent radical prostatectomy and pelvic lymphadenectomy, which revealed a pT3b pN1 carcinoma with infiltrated resection margins. Three months later, the prostate-specific antigen level was 1.4 ng/ml, and a local recurrence was suspected by ultrasound; consequently, a 68Ga-prostate-specific membrane antigen (PSMA) PET/CT was performed. This examination seemed to confirm the local recurrence, a right pelvic lymph node metastasis, and a hepatic metastasis. However, ultrasound with contrast medium could not confirm the metastatic spread to the liver. In palliative intention, radiotherapy of the pelvis was done. After 50 Gy, the supposed recurrence had markedly shrunk, and an additional boost dose with 16.2 Gy was applied. Two years later, the patient is still free of disease. Due to this clinical development, we doubt the diagnosis of a fulminant progression of the prostate cancer as suspected by PSMA-PET/CT. Instead, we suspect a recurrence of the previously proven sarcoidosis leading to false-positive results. Our focus in this report is on the interaction between PSMA-PET/CT and sarcoidosis. Another report on a case of sarcoidosis of the spleen seems to confirm this possibility [Kobe et al: Clin Nucl Med 2015;40: 897-898].