Interdisciplinary consensus statement on indication and application of a hydrogel spacer for prostate radiotherapy based on experience in more than 250 patients.

BACKGROUND: The aim of the study was to reach a consensus on indication and application of a hydrogel spacer based on multicentre experience and give new users important information to shorten the learning curve for this innovative technique. METHODS: The interdisciplinary meeting was attended by radiation oncologists and urologists, each with experience of 23 - 138 hydrogel injections (SpaceOAR®) in prostate cancer patients before dose-escalated radiotherapy. User experience was discussed and questions were defined to comprise practical information relevant for successful hydrogel injection and treatment. Answers to the defined key questions were generated. Hydrogel-associated side effects were collected to estimate the percentage, treatment and prognosis of potential risks. RESULTS: The main indication for hydrogel application was dose-escalated radiotherapy for histologically confirmed low or intermediate risk prostate cancer. It was not recommended in locally advanced prostate cancer. The injection or implantation was performed under transrectal ultrasound guidance via the transperineal approach after prior hydrodissection. The rate of injection-related G2-toxicity was 2% (n = 5) in a total of 258 hydrogel applications. The most frequent complication (n = 4) was rectal wall penetration, diagnosed at different intervals after hydrogel injection and treated conservatively. CONCLUSIONS: A consensus was reached on the application of a hydrogel spacer. Current experience demonstrated feasibility, which could promote initiation of this method in more centres to reduce radiation-related gastrointestinal toxicity of dose-escalated IGRT. However, a very low rate of a potential serious adverse event could not be excluded. Therefore, the application should carefully be discussed with the patient and be balanced against potential benefits.

Neoadjuvant hormonal therapy and external-beam radiotherapy versus external-beam irradiation alone for prostate cancer. A quality-of-life analysis.

PURPOSE: To evaluate the impact of neoadjuvant hormonal therapy (NHT) on quality of life after external-beam radiotherapy (EBRT) for prostate cancer. PATIENTS AND METHODS: A group of 170 patients (85 with and 85 without NHT) has been surveyed prospectively before EBRT (70.2-72 Gy), at the last day of EBRT, a median time of 2 months and 15 months after EBRT using a validated questionnaire (Expanded Prostate Cancer Index Composite). Pairs with and without NHT (median treatment time of 3.5 months before EBRT) were matched according to the respective planning target volume and prostate volume. RESULTS: Before EBRT, significantly lower urinary function/bother, sexual function and hormonal function/bother scores were found for patients with NHT. More than 1 year after EBRT, only sexual function scores remained lower. In a multivariate analysis, NHT and adjuvant hormonal therapy (HT) versus NHT only (hazard ratio 14; 95% confidence interval 2.7-183; p = 0.02) and luteinizing hormone-releasing hormone (LHRH) agonists versus antiandrogens (hazard ratio 3.6; 95% confidence interval 1.1-12; p = 0.04) proved to be independent risk factors for long-term erectile dysfunction (no or very poor ability to have an erection). CONCLUSION: With the exception of sexual function (additional adjuvant HT and application of LHRH analog independently adverse), short-term NHT was not found to decrease quality of life after EBRT for prostate cancer.

Impact of age and comorbidities on health-related quality of life for patients with prostate cancer: evaluation before a curative treatment.

BACKGROUND: Interpretation of comparative health-related quality of life (HRQOL) studies following different prostate cancer treatments is often difficult due to differing patient ages. Furthermore, age-related changes can hardly be discriminated from therapy-related changes. The evaluation of age-and comorbidity-related changes was in focus of this study. METHODS: HRQOL of 528 prostate cancer patients was analysed using a validated questionnaire (Expanded Prostate Cancer Index Composite) before a curative treatment. Patients were divided into age groups 75 years. The impact of specific comorbidities and the Charlson Comorbidity Index (CCI) were evaluated. The questionnaire comprises 50 items concerning the urinary, bowel, sexual and hormonal domains for function and bother. For assessment of sexual and hormonal domains, only patients without prior hormonal treatment were included (n = 336). RESULTS: Urinary incontinence was observed increasingly with higher age (mean function scores of 92/88/85/87 for patients 75 years) complete urinary control in 78%/72%/64%/58% (p < 0.01). Sexual function scores decreased particularly (48/43/35/30), with erections sufficient for intercourse in 68%/50%/36%/32% (p < 0.01) a decrease of more than a third comparing patients 75 years; p < 0.05). A multivariate analysis revealed an independent influence of both age and comorbidities on urinary incontinence, specifically diabetes on urinary bother, and both age and diabetes on sexual function/bother. Rectal domain scores were not significantly influenced by age or comorbidities. A CCI>5 particularly predisposed for lower urinary and sexual HRQOL scores. CONCLUSION: Urinary continence and sexual function are the crucial HRQOL domains with age-related and independently comorbidity-related decreasing scores. The results need to be considered for the interpretation of comparative studies or longitudinal changes after a curative treatment.

Toxicity profile with a large prostate volume after external beam radiotherapy for localized prostate cancer.

PURPOSE: To assess the impact of prostate volume on health-related quality of life (HRQOL) before and at different intervals after radiotherapy for prostate cancer. METHODS AND MATERIALS: A group of 204 patients was surveyed prospectively before (Time A), at the last day (Time B), 2 months after (Time C), and 16 months (median) after (Time D) radiotherapy, with a validated questionnaire (Expanded Prostate Cancer Index Composite). The group was divided into subgroups with a small (11-43 cm(3)) and a large (44-151 cm(3)) prostate volume. RESULTS: Patients with large prostates presented with lower urinary bother scores (median 79 vs. 89; p = 0.01) before treatment. Urinary function/bother scores for patients with large prostates decreased significantly compared to patients with small prostates due to irritative/obstructive symptoms only at Time B (pain with urination more than once daily in 48% vs. 18%; p < 0.01). Health-related quality of life did not differ significantly between both patient groups at Times C and D. In contrast to a large prostate, a small initial bladder volume (with associated higher dose-volume load) was predictive for lower urinary bother scores both in the acute and late phase; at Time B it predisposed for pollakiuria but not for pain. Patients with neoadjuvant hormonal therapy reached significantly lower HRQOL scores in several domains (affecting only incontinence in the urinary domain), despite a smaller prostate volume (34 cm(3) vs. 47 cm(3); p < 0.01). CONCLUSIONS: Patients with a large prostate volume have a great risk of irritative/obstructive symptoms (particularly dysuria) in the acute radiotherapy phase. These symptoms recover rapidly and do not influence long-term HRQOL.

Health-related quality of life after adjuvant and salvage postoperative radiotherapy for prostate cancer - a prospective analysis.

BACKGROUND AND PURPOSE: The aim of the study was to analyze health-related quality of life changes after postoperative radiotherapy (RT) for prostate cancer. MATERIALS AND METHODS: A group of 101 patients has been surveyed prospectively before (time A), at the last day (B), two months after (C) and >1 year after (D) RT using a validated questionnaire (Expanded Prostate Cancer Index Composite) with urinary, bowel, sexual and hormonal domains. The prostatic fossa was treated with a four-field box technique up to a total dose of 66.6 Gy. RESULTS: While median urinary scores reached baseline levels already two months after radiotherapy (function/bother scores at time A-B-C-D: 94/89-89/75-94/89-94/89; A vs. B: p<0.01), bowel problems needed a longer time to recover (function/bother scores at time A-B-C-D: 96/100-85/89-88/93-96/100; A vs. B/C: p<0.01). Greater bladder volumes inside specific isodoses were associated with temporary significantly lower urinary bother scores and chronically lower urinary incontinence scores. Only 7% of patients reported of erections firm enough for intercourse before RT, so that RT-associated sexual toxicity played a minor role. CONCLUSIONS: In contrast to bowel symptoms, acute urinary problems recover very soon after the end of postoperative RT. After >1 year, only minor HRQOL changes occurred in comparison to baseline scores.

Sequencing chemotherapy and radiotherapy in locoregional advanced breast cancer patients after mastectomy - a retrospective analysis.

BACKGROUND: Combined chemo- and radiotherapy are established in breast cancer treatment. Chemotherapy is recommended prior to radiotherapy but decisive data on the optimal sequence are rare. This retrospective analysis aimed to assess the role of sequencing in patients after mastectomy because of advanced locoregional disease. METHODS: A total of 212 eligible patients had a stage III breast cancer and had adjuvant chemotherapy and radiotherapy after mastectomy and axillary dissection between 1996 and 2004. According to concerted multi-modality treatment strategies 86 patients were treated sequentially (chemotherapy followed by radiotherapy) (SEQgroup), 70 patients had a sandwich treatment (SW-group) and 56 patients had simultaneous chemoradiation (SIM-group) during that time period. Radiotherapy comprised the thoracic wall and/or regional lymph nodes. The total dose was 45-50.4 Gray. As simultaneous chemoradiation CMF was given in 95.4% of patients while in sequential or sandwich application in 86% and 87.1% of patients an anthracycline-based chemotherapy was given. RESULTS: Concerning the parameters nodal involvement, lymphovascular invasion, extracapsular spread and extension of the irradiated region the three treatment groups were significantly imbalanced. The other parameters, e.g. age, pathological tumor stage, grading and receptor status were homogeneously distributed. Looking on those two groups with an equally effective chemotherapy (EC, FEC), the SEQ- and SW-group, the sole imbalance was the extension of LVI (57.1 vs. 25.6%, p < 0.0001).5-year overall- and disease free survival were 53.2%/56%, 38.1%/32% and 64.2%/50%, for the sequential, sandwich and simultaneous regime, respectively, which differed significantly in the univariate analysis (p = 0.04 and p = 0.03, log-rank test). Also the 5-year locoregional or distant recurrence free survival showed no significant differences according to the sequence of chemo- and radiotherapy. In the multivariate analyses the sequence had no independent impact on overall survival (p = 0.2) or disease free survival (p = 0.4). The toxicity, whether acute nor late, showed no significant differences in the three groups. The grade III/IV acute side effects were 3.6%, 0% and 3.5% for the SIM-, SW- and SEQ-group. By tendency the SIM regime had more late side effects. CONCLUSION: No clear advantage can be stated for any radio- and chemotherapy sequence in breast cancer therapy so far. This could be confirmed in our retrospective analysis in high-risk patients after mastectomy. The sequential approach is recommended according to current guidelines considering a lower toxicity.

Active breathing control (ABC): determination and reduction of breathing-induced organ motion in the chest.

PURPOSE: Extensive radiotherapy volumes for tumors of the chest are partly caused by interfractional organ motion. We evaluated the feasibility of respiratory observation tools using the active breathing control (ABC) system and the effect on breathing cycle regularity and reproducibility. METHODS AND MATERIALS: Thirty-six patients with unresectable tumors of the chest were selected for evaluation of the ABC system. Computed tomography scans were performed at various respiratory phases starting at the same couch position without patient movement. Threshold levels were set at minimum and maximum volume during normal breathing cycles and at a volume defined as shallow breathing, reflecting the subjective maximal tolerable reduction of breath volume. To evaluate the extent of organ movement, 13 landmarks were considering using commercial software for image coregistration. In 4 patients, second examinations were performed during therapy. RESULTS: Investigating the differences in a normal breathing cycle versus shallow breathing, a statistically significant reduction of respiratory motion in the upper, middle, and lower regions of the chest could be detected, representing potential movement reduction achieved through reduced breath volume. Evaluating interfraction reproducibility, the mean displacement ranged between 0.24 mm (chest wall/tracheal bifurcation) to 3.5 mm (diaphragm) for expiration and shallow breathing and 0.24 mm (chest wall) to 5.25 mm (diaphragm) for normal inspiration. CONCLUSIONS: By modifying regularity of the respiratory cycle through reduction of breath volume, a significant and reproducible reduction of chest and diaphragm motion is possible, enabling reduction of treatment planning margins.

Evaluation of source displacement and dose--volume changes after permanent prostate brachytherapy with stranded seeds.

BACKGROUND AND PURPOSE: The aim of the study was to analyze source displacements and dose-volume changes in the first month after a permanent implant. MATERIALS AND METHODS: In 51 consecutive patients, CT scans were performed at the postoperative day (day 1) and one month (day 30) after an (125)I implant with stranded seeds. Seed positions were determined relative to pelvic bones for five seeds at the base and five seeds at the apex for each patient (n=510) and compared. To verify these results, treatment margins (TM=distance of prescription isodose to prostate) and displacements of the prostate surface (anterior/posterior/right/left/superior/inferior) relative to pelvic bones were measured. RESULTS: Seed positions have moved significantly between day 1 and 30 in the posterior (mean 1.0mm; p<0.001) and inferior (mean 3.8mm; p<0.001) directions. TM increased particularly at the posterior (mean 2.2mm; p<0.001) and apical (median 3.0mm; p<0.001) prostate contour with decreasing oedema. With a stable apex position and a mean inward posterior surface displacement of 1.1mm (p<0.001) relative to pelvic bones, seed displacements could be well correlated with prescription isodose displacements (Pearson correlation coefficients >or=0.81; p<0.001). CONCLUSIONS: Both changes of prostate volume and seed displacements need to be considered to explain dosimetric changes after permanent prostate brachytherapy.

Bladder extension variability during pelvic external beam radiotherapy with a full or empty bladder.

BACKGROUND AND PURPOSE: Varying bladder fillings during radiotherapy lead to a changing dose-volume load to the bladder and adjacent structures. The aim of the study was to compare the extent of bladder wall movements during parallel series with full bladder (FB) and empty bladder (EB). MATERIALS AND METHODS: Three hundred and forty serial computed tomography (CT) scans were performed in 50 patients scheduled for primary and postoperative radiotherapy for prostate cancer. Each patient underwent two CT scans (with FB and EB) before and 2-3 times during radiotherapy. Displacements of the bladder wall were compared and correlated with changing bladder fillings. RESULTS: The variability of FB was larger compared to EB volume (standard deviation of 124 cc and 56 cc; p<0.01), but significant bladder wall displacement variabilities were only found at the anterior and superior borders. Within a bladder volume range between -100 and +200 ml relative to the FB planning scan, the mean bladder wall displacement remained < 5 mm at the inferior, lateral, and posterior borders - as opposed to 15 and 21 mm at the anterior and superior borders. CONCLUSIONS: Treating the pelvis with EB compared to FB, bladder wall displacement can be only reduced at the superior and anterior borders. FB wall displacements are comparable with EB displacements at all other borders.

Postoperative radiotherapy for prostate cancer : evaluation of target motion and treatment techniques (intensity-modulated versus conformal radiotherapy).

PURPOSE: To determine the extent of target motion in postprostatectomy radiotherapy (RT) and the value of intensity-modulated radiotherapy (IMRT) compared to three-dimensional conformal radiotherapy (3D-CRT). PATIENTS AND METHODS: 20 patients underwent CT scans in supine position with both a full bladder (FB) and an empty bladder (EB) before RT and at three dates during the RT series. Displacements of the CTV (clinical target volume) center of mass and the posterior border were determined. 3D-CRT and IMRT treatment plans were compared regarding homogeneity, conformity, and dose to organs at risk. RESULTS: In the superior-inferior direction, larger displacements were found for EB compared to FB scans; anterior-posterior and right-left displacements were similar. With an initial rectum volume of < 115 cm(3), 90% of displacements at the posterior border were within a margin of 6 mm. The non-target volume irradiated in the high-dose area doubled in 3D-CRT versus IMRT plans (80 cm(3) vs. 38 cm(3) encompassed by the 95% isodose). Bladder dose was significantly lower with IMRT, but no advantage was found for the integral rectal dose. An adequate bladder filling was paramount to reduce the dose to the bladder. CONCLUSION: Postprostatectomy RT can be recommended with FB due to an improved CTV position consistency and a lower dose to the bladder. With improved non-target tissue and bladder volume sparing, IMRT is an option for dose escalation. However, this analysis did not find an advantage concerning the integral rectal dose with IMRT versus 3D-CRT.

Sequential (gemcitabine/vinorelbine) and concurrent (gemcitabine) radiochemotherapy with FDG-PET-based target volume definition in locally advanced non-small cell lung cancer: first results of a phase I/II study.

BACKGROUND: The aim of the study was to determine the maximal tolerated dose (MTD) of gemcitabine every two weeks concurrent to radiotherapy, administered during an aggressive program of sequential and simultaneous radiochemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC) and to evaluate the efficacy of this regime in a phase II study. METHODS: 33 patients with histologically confirmed NSCLC were enrolled in a combined radiochemotherapy protocol. 29 patients were assessable for evaluation of toxicity and tumor response. Treatment included two cycles of induction chemotherapy with gemcitabine (1200 mg/m2) and vinorelbine (30 mg/m2) at day 1, 8 and 22, 29 followed by concurrent radiotherapy (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine every two weeks at day 43, 57 and 71. Radiotherapy planning included [18F] fluorodeoxyglucose positron emission tomography (FDG PET) based target volume definition. 10 patients were included in the phase I study with an initial gemcitabine dose of 300 mg/m2. The dose of gemcitabine was increased in steps of 100 mg/m2 until the MTD was realized. RESULTS: MTD was defined for the patient group receiving gemcitabine 500 mg/m2 due to grade 2 (next to grade 3) esophagitis in all patients resulting in a mean body weight loss of 5 kg (SD = 1.4 kg), representing 8% of the initial weight. These patients showed persisting dysphagia 3 to 4 weeks after completing radiotherapy. In accordance with expected complications as esophagitis, dysphagia and odynophagia, we defined the MTD at this dose level, although no dose limiting toxicity (DLT) grade 3 was reached. In the phase I/II median follow-up was 15.7 months (4.1 to 42.6 months). The overall response rate after completion of therapy was 64%. The median overall survival was 19.9 (95% CI: [10.1; 29.7]) months for all eligible patients. The median disease-free survival for all patients was 8.7 (95% CI: [2.7; 14.6]) months. CONCLUSION: After induction chemotherapy, the maximum tolerated dose and frequency of gemcitabine was defined at 500 mg/m2 every two weeks in three cycles during a maximum of 7 weeks of thoracic radiotherapy for the phase II study. This regimen represents an effective and tolerable therapy in the treatment of NSCLC.

pO polarography, contrast enhanced color duplex sonography (CDS), [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography: validated methods for the evaluation of therapy-relevant tumor oxygenation or only bricks in the puzzle of tumor hypoxia?

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 CT-controlled 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 < or = 2.5, < or = 5.0 and < or = 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 x 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 < or = 2.5, < or = 5.0 and < or = 10.0 mmHg, as well as median pO2), CPD and FMISOT/M. Only a slight correlation between TP and the fraction of pO2 values < or = 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.

Prostate position variability and dose-volume histograms in radiotherapy for prostate cancer with full and empty bladder.

PURPOSE: To evaluate prostate position variability and dose-volume histograms in prostate radiotherapy with full bladder (FB) and empty bladder (EB). METHODS AND MATERIALS: Thirty patients underwent planning computed tomography scans in a supine position with FB and EB before and after 4 and 8 weeks of radiation therapy. The scans were matched by alignment of pelvic bones. Displacements of the prostate/seminal vesicle organ borders and center of mass were determined. Treatment plans (FB vs. EB) were compared. RESULTS: Compared with the primary scan, FB volume varied more than EB volume (standard deviation, 106 cm3 vs. 47 cm3), but the prostate/seminal vesicle center of mass position variability was the same (> 3 mm deviation in right-left, anterior-posterior, and superior-inferior directions in 0, 41%, and 33%, respectively, with FB vs. 0, 44%, and 33% with EB). The bladder volume treated with 90% of the prescription dose was significantly larger with EB (39% +/- 14% vs. 22% +/- 10%; p < 0.01). Bowel loops received > or = 90% of prescription dose in 37% (3% with FB; p < 0.01). CONCLUSION: Despite the larger variability of bladder filling, prostate position stability was the same with FB compared with EB. An increased amount of bladder volume in the high-dose region and a higher dose to bowel loops result from treatment plans with EB.

Low-grade toxicity after conformal radiation therapy for prostate cancer--impact of bladder volume.

PURPOSE: To assess the impact of dose-volume histogram parameters on low-grade toxicity after radiotherapy for prostate cancer. METHODS AND MATERIALS: Eighty patients have been surveyed prospectively before (time A), at the last day (B), 2 months after (C), and 16 months (median) after (D) radiotherapy (70.2 Gy) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Dose-volume histograms were correlated with urinary and bowel function/bother scores. RESULTS: The initial bladder volume and the percentage of the bladder volume receiving 10%-90% of the prescription dose significantly correlated with urinary function/bother scores (significant cutoff levels found for all dose levels). Pain with urination proved to be mainly an acute problem, subsiding faster for patients with larger bladder volumes and smaller volumes inside particular isodose lines. At time D, persisting problems with smaller initial bladder volumes were a weak stream and an increased frequency of urination. Though bladder volume and planning target volume both independently have an influence on dose-volume histogram parameters for the bladder, bladder volume plays the decisive role for urinary toxicity. CONCLUSIONS: The patient's ability to fill the bladder has a major impact on the dose-volume histogram and both acute and late urinary toxicity.

Influence of the initial rectal distension on posterior margins in primary and postoperative radiotherapy for prostate cancer.

BACKGROUND AND PURPOSE: The aim of the study was to define the effect of different rectum fillings in the planning CT study on the posterior clinical target volume (CTV) displacements (PD) in primary and postoperative radiotherapy (RT) for prostate cancer. MATERIALS AND METHODS: Fifty patients underwent CT scans in supine position with a full bladder and an empty bladder before RT and at several points in time during the treatment. PD were determined depending on the initial rectum volume (RV), average cross-sectional rectal area (CSA), and the rectal diameter at the level of the bladder neck (RD). RESULTS: Posterior CTV motion was not found to be minimal with a particularly small initial rectum filling. Steeply increasing PD resulted for patients with RV>120cm(3), CSA>12cm(2), and RD>4.5cm. While below these critical values a posterior margin of 6mm/9mm allowed to cover 80%/90% of displacements, 18mm/24mm were needed for patients with larger rectum fillings. No correlation of increasing rectum distension with increasing PD was found at the apex level. PD could not be reduced by voiding the bladder. CONCLUSIONS: Defining the posterior margin in prostate RT, the initial rectum distension and the superior-inferior CTV level has to be considered. Patients with large initial rectum fillings have preferentially the need for repeated planning CT scans or image-guided RT.

Dose-volume impact in high-dose-rate Iridium-192 brachytherapy as a boost to external beam radiotherapy for localized prostate cancer--a phase II study.

BACKGROUND AND PURPOSE: Evaluation of dose-volume-time-related factors in 64 patients treated with high-dose-rate brachytherapy (HDR-BT) as a boost to external beam radiotherapy (EBRT) for localized prostate cancer. PATIENTS AND METHODS: Clinical parameters were correlated with morbidity scores of the EPIC (Expanded Prostate Cancer Index) questionnaire. Median time after radiotherapy (HDR-BT up to 18 Gy in two fractions and EBRT up to a median dose of 50.4 Gy) was 1.5 and 3 years (first and second questionnaire). RESULTS: A significant impact of a urethra D1 exceeding 15 Gy in at least one HDR fraction concerning urinary morbidity and a rectum D1 exceeding 6 Gy to the rectal mucosa in the first and second HDR fraction concerning the rectal bleeding rate was found. A higher number of needles was associated with lower urinary and bowel scores after 1.5 years. A prostate length >4.8 cm and a longer duration of EBRT (independently of the dose) predisposed for lower urinary and bowel scores. In contrast to a urethra D1 > 15 Gy as an independent factor, a rectum D1 > 6 Gy per HDR fraction correlated with a higher number of needles and an increased prostate length. CONCLUSIONS: To minimize morbidity in HDR-BT for prostate cancer, a maximum dose to the urethra of 15 Gy and a maximum dose to the rectal mucosa of 6 Gy is advisable. Treatment- and patient-related factors have a major impact on toxicity.

FDG--a marker of tumour hypoxia? A comparison with [18F]fluoromisonidazole and pO2-polarography in metastatic head and neck cancer.

PURPOSE: Experimental data suggest that the accumulation of [(18)F]fluorodeoxyglucose (FDG) in malignant tumours is related to regional hypoxia. The aim of this study was to evaluate the clinical potential of FDG positron emission tomography (PET) to assess tumour hypoxia in comparison with [(18)F]fluoromisonidazole (FMISO) PET and pO(2)-polarography. METHODS: Twenty-four patients with head and neck malignancies underwent FDG PET, FMISO PET, and pO(2)-polarography within 1 week. Parameters of pO(2)-polarography were the relative frequency of pO(2) readings

[18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography in response evaluation after chemo-/radiotherapy of non-small-cell lung cancer: a feasibility study.

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.

Evaluation of tumor oxygenation by color duplex sonography: a new approach.

OBJECTIVE: Description of a new noninvasive method for the evaluation of tissue oxygenation in head and neck cancer. STUDY DESIGN AND SETTING: Prospective nonrandomized controlled study in an academic medical center on 20 patients with neck metastases of head and neck cancer. Metastases were investigated using color duplex sonography and pO2 histography. The vascularization in sonography was quantitatively evaluated by color pixel density and compared to the pO2 values of the same nodes. RESULTS: The correlation between vascularization and flow velocity was 0.71. For the mean/median pO2 -values and for the pO2 readings <10.0 mmHg correlations were r = 0.65 / 0.76 and 0.71. CONCLUSION: This sonographic method allows a safe and reliable evaluation of oxygenation in metastases of head and neck cancer. SIGNIFICANCE: The new approach is an alternative to pO2 histography and may play a future role in the planning of radiotherapy in the neck.

Dose-volume histogram evaluation of prone and supine patient position in external beam radiotherapy for cervical and endometrial cancer.

BACKGROUND AND PURPOSE: To evaluate the influence of patient positioning on dose-volume histograms of organs at risk in external beam radiotherapy for cervical and endometrial cancer. MATERIALS AND METHODS: In 20 patients scheduled for definitive (7) or postoperative (13) external beam radiotherapy of the pelvis treatment planning CT scans were performed in supine and prone (belly board) positions. After volume definition of target and organs at risk treatment plans were calculated applying the four-field box technique. The dose-volume histograms of organs at risk were compared. RESULTS: Radiotherapy in prone position causes a reduction of the bladder portion (mean 15%, p<0.001) and an increase of the rectum portion (mean 11%, p<0.001) within the 90% isodose. A reduction of the bowel portion could only be observed in postoperatively treated patients (mean 13%, p<0.001). In definitive radiotherapy the target volume increases in supine position (mean 7%, p=0.02) due to an anterior tumour/uterus movement, so that bowel portions within the 90% isodose are similar. The bladder filling correlates with a reduction of bladder and bowel (postoperatively treated patients) dose. CONCLUSIONS: External beam radiotherapy of the pelvis should be performed in prone position in postoperative patients because of best bowel protection. Considering the additional HDR brachytherapy rectum protection takes the highest priority in definitive treatment-the requirements are best met in supine position. An adequate bladder filling is important to reduce the irradiated bladder and bowel volumes.