VMAT techniques for lymph node-positive left sided breast cancer.

PURPOSE: To investigate the plan quality of two different volumetric modulated arc therapy (VMAT) techniques for lymph node-positive left-sided breast cancer. METHODS: Two VMAT plans were generated for 10 lymph node-positive left-sided breast cancer patients: one plan using one single segment of a full rotation, typically an arc segment of 230° (1s-VMAT); and a second plan consisting of 2 small tangential arc segments of about 50° (2s-VMAT). For plan comparison, various dose and dose volume metrics (Dmean, D98%, D2% for target volumes, D2%, Dmean and Vx% for organs at risk (OAR)) were evaluated. RESULTS: Both techniques fulfilled both clinical target dose and OAR goals. 1s-VMAT achieved a slightly better homogeneity and better target coverage (D2%= 54.2 ± 0.7 Gy, D98%= 30.3 ± 1.8 Gy) compared to 2s-VMAT (D2%= 55.0 ± 1.1 Gy, D98%= 29.9 ± 1.7 Gy). For geometrical reasons, OAR sparing was noticeable but not significant better using 2s-VMAT, particularly heart and contralateral breast. The heart received a mean dose of 4.4 ± 0.8 Gy using 1s-VMAT and 3.3 ± 1.0 Gy using 2s-VMAT; the contralateral breast received 1.5 ± 0.3 Gy and 0.9 ± 0.3 Gy, respectively. CONCLUSIONS: A VMAT technique based on two small tangential arc segments enables improved OAR sparing; the differences between the two techniques in target coverage and homogeneity are minor. Patient age and -anatomy must be considered for each individual case when deciding which technique to be used.

Neurosurgical treatment strategies in childhood craniopharyngiomas: is less more?

OBJECTIVE: Craniopharyngiomas in children are typically present in combination with heterogeneous clinical and neuroradiological findings. It has remained highly challenging to choose the optimal treatment strategy with regard to local tumor control and clinical outcome. Here, we analyze different treatment methods and evaluate the results. METHODS: We performed a detailed retrospective evaluation of 32 children <18 years old treated for craniopharyngioma between 1990 and 2008 at the University Hospital Freiburg. Three patient groups could be identified: children treated with microsurgical resection (n=17), with stereotactic cyst drainage and radiotherapy (n=7), and with various combined approaches (n=8). RESULTS: Six of seven children treated with stereotactic cyst punction and radiation are still alive. All of them are in an age-appropriate neuropsychological condition. Two of seven patients in this group have tumor recurrences. Fourteen of the 17 children treated with microsurgical resection show tumor recurrences (p=0.02). Fifteen are alive, and ten out of 17 show an age-appropriate neuropsychological development. The 8.5 years freedom from progression differed from 24% in the resection group to 71% in the cohort treated with stereotactic cyst drainage and radiotherapy (p=0.05). In the third group treated with various approaches, three of eight patients were treated for cystic recurrence. The average follow-up is 5.5 years. CONCLUSIONS: Based on our nonrandomized retrospective monocentric analysis, patients treated with less invasive stereotactic and radiotherapeutical methods have a more favorable long-term clinical outcome compared to children treated with a more radical microsurgical approach. Due to the possible implications of these results, further prospective trials should be encouraged.

Secular trends in pediatric bloodstream infections over a 20-year period at a tertiary care hospital in Germany.

OBJECTIVE: Over the last 20 years, a number of medical innovations with impact on the incidence of bacterial and fungal bloodstream infections (BSIs) in children have been developed and implemented. Although appropriate empirical antimicrobial therapy is a prerequisite to the successful treatment of BSIs, to date, epidemiological data on long-term microbiological trends in BSIs of hospitalized children have not been available. METHODS: Two cohorts of pediatric patients who were hospitalized in a single-center tertiary care hospital in Germany over a 20-year time span (period A from 1985 to 1995 vs. period B from 1997 to 2006) were retrospectively analyzed and compared with respect to the epidemiology and microbiology of BSIs. RESULTS: A total of 1,646 cases of monomicrobial BSIs were detected. The rate of positive blood culture results dropped from 4.5% in period A to 2.0% in period B. The proportion of gram-positive vs. gram-negative pathogens recovered from blood cultures remained stable. Among gram-positive pathogens, an increase in enterococci (3.3% vs. 8.2%) and in coagulase-negative staphylococci (CoNS) (22.9 vs. 28.2%) was observed. In contrast, BSIs caused by Staphylococcus aureus (16.4% vs. 11.7%), Streptococcus agalactiae (4.9% vs. 2.1%), Haemophilus influenzae (7.3% vs. 0.7%), and Neisseria meningitidis (1.9% vs. 0.5%) diminished. In analyzing subgroups, an increase of enterococcal and CoNS infections was noted among patients with immunosuppression and neonatal early-onset sepsis (EOS), while a decrease was found among late-onset sepsis (LOS) cases with S. viridans. Notably, aminopenicillin-resistant enterococci and aminopenicillin- and fluoroquinolone-resistant Enterobacteriaceae all increased over time, while the overall resistance pattern was still favorable. The overall mortality rate of BSIs decreased (5.2% vs. 2.6%). CONCLUSIONS: Over the 20-year study period, the spectrum of specific microorganisms among BSIs shifted, with opportunistic pathogens becoming predominant. Despite an increase in the proportion of antibiotic-resistant organisms, however, the mortality rate decreased.

Religious belief as a coping strategy: an explorative trial in patients irradiated for head-and-neck cancer.

PURPOSE: To explore the role of religious belief in coping with disease symptoms and treatment-related side effects in patients with head-and-neck cancer under radiotherapy. PATIENTS AND METHODS: Prospectively collected data were used with a cohort of head-and-neck cancer patients treated by radiotherapy and epoetin beta or placebo within a double-blind multicenter trial. All patients were divided into believers and nonbelievers. Answers to a quality of life questionnaire at four points in time during radiotherapy were analyzed according to both groups. Clinical parameters and therapy side effects were controlled regularly. RESULTS: 62.1% of the patients (66/105) sent back a baseline questionnaire discriminating between believers and nonbelievers. For 34.2% (40/105) data of all four measures could be obtained. On average, believers felt better in all categories of side effects at all points of time before, during and directly after therapy. CONCLUSION: Religious faith seems to play an important role in coping strategies of radiotherapy patients. More research in this area would be worthwhile.

Anemia and long-term outcome in adjuvant and neoadjuvant radiochemotherapy of stage II and III rectal adenocarcinoma: the Freiburg experience (1989-2002).

AIM: To evaluate the long-term outcome of standard 5-FU based adjuvant or neoadjuvant radiochemotherapy and to identify the predictive factors, especially anemia before and after radiotherapy as well as hemoglobin increase or decrease during radiotherapy. METHODS: Two hundred and eighty-six patients with Union International Contre Cancer (UICC) stage II and III rectal adenocarcinomas, who underwent resection by conventional surgical techniques (low anterior or abdominoperineal resection), received either postoperative (n=233) or preoperative (n=53) radiochemotherapy from January 1989 until July 2002. Overall survival (OAS), cancer-specific survival (CSS), disease-free survival (DFS), local-relapse-free (LRS) and distant-relapse-free survival (DRS) were evaluated using Kaplan-Meier, Log-rank test and Cox's proportional hazards as statistical methods. Multivariate analysis was used to identify prognostic factors. Median follow-up time was 8 years. RESULTS: Anemia before radiochemotherapy was an independent prognostic factor for improved DFS (risk ratio 0.76, P=0.04) as well as stage, grading, R status (free radial margins), type of surgery, carcinoembryonic antigen (CEA) levels, and gender. The univariate analysis revealed that anemia was associated with impaired LRS (better local control) but with improved DFS. In contrast, hemoglobin decrease during radiotherapy was an independent risk factor for DFS (risk ratio 1.97, P=0.04). During radiotherapy, only 30.8% of R0-resected patients suffered from hemoglobin decrease compared to 55.6% if R1/2 resection was performed (P=0.04). The 5-year OAS, CSS, DFS, LRS and DRS were 47.0%, 60.0%, 41.4%, 67.2%, and 84.3%, respectively. Significant differences between preoperative and postoperative radiochemotherapy were not found. CONCLUSION: Anemia before radiochemotherapy and hemoglobin decrease during radiotherapy have no predictive value for the outcome of rectal cancer. Stage, grading, R status (free radial margins), type of surgery, CEA levels, and gender have predictive value for the outcome of rectal cancer.

Gastrointestinal cancer web sites: how do they address patients' concerns?

BACKGROUND: We studied the quality of web sites containing information on gastrointestinal cancer, focusing on the way these web sites dealt with the special concerns of these patients. MATERIALS AND METHODS: Searching the Internet for German-language gastroenterological cancer web sites, we collected 9,947 web pages from 14 search engines. Evaluation was done with a 36-item questionnaire. Information quality, availability of the web sites, and web site attributes considering patients' concerns and potential embarrassment were analyzed using a scoring system. RESULTS: Belonging to 165 web sites, 1,763 of 9,947 (17.7%) web pages found by search engines provided relevant information. Five hundred forty-seven (5.5%) hits were partly relevant, and 7,637 (76.8%) were irrelevant or not available. Most web sites reported about surgery (92.1%), chemotherapy (88.5%), and radiotherapy (73.9%). Of the web sites, 46.7% (n=77), 34.6% (n=57), and 21.8% (n=36) gave information about the author(s) itself, their qualifications, and references of their information, respectively. Search engines ranked web sites giving no information on evidence-based medicine higher than other web sites, whereas web sites providing this information accurately showed higher link popularities. Patients' concerns and potential embarrassment were best addressed by gastrointestinal web sites initiated by private individuals or web sites directed to both a patient and physician audience. CONCLUSIONS: With regard to gastrointestinal cancer web sites, many search engines may be ineffective, and patient emotional needs and concerns are often disregarded. Also, physicians should guide their patients through the Internet to find high-quality information and use link-popularity-based search strategies.

Spectrophotometric skin measurements correlate with EORTC/RTOG-common toxicity criteria.

PURPOSE: It was investigated whether the elementary EORTC/RTOG-CTC score (Common Toxicity Criteria) for radiotherapy skin reactions correlates with spectrophotometric measurements of the skin color. PATIENTS, MATERIAL, AND METHODS: In 41 patients irradiated for unilateral breast cancer the regular scoring by CTC was done during radiotherapy. In parallel, a total of 4,920 spectrophotometric measurements to determine the skin color were performed at baseline, at the beginning of radiotherapy, and at 20, 40 and 60 Gy. The nonirradiated contralateral breast was used for control measurements. RESULTS: As expected, the skin color (especially red) depended on the radiation dose applied to the skin. The objective spectrophotometric measurements were found to correlate well with the subjective CTC scores. CONCLUSION: For classification of acute radiation toxicity there seems to be no need to replace the common CTC scoring by technical methods.

Is older age associated with a worse prognosis due to different patterns of care? A long-term study of 1346 patients with glioblastomas or brain metastases.

BACKGROUND: The objective of this study was to find out whether the worse prognosis of older patients with primary or metastatic brain tumors can be explained by different patterns of care compared with younger patients. METHODS: A data base that included 430 patients with glioblastomas and 916 patients with brain metastases who underwent radiotherapy at the author's hospital between 1980 and 2000 was analyzed. Patterns of care were compared for different age groups using the chi-square test. RESULTS: In both patient groups, age turned out to be an independent risk factor. Older age was associated with worse overall survival. Independent of the cut-off age (< 50 years vs. > or = 50 years, < 60 years vs. > or = 60 years, < 65 years vs. > or = 65 years, and < 70 years vs. > or = 70 years), there were no statistically significant differences between the age groups concerning the use of different imaging modalities (computed tomography scans vs. magnetic resonance imaging), type of surgery (none vs. biopsy vs. resection), waiting time for radiotherapy (< median vs. > or = median), radiotherapy treatment planning (simulator-based vs. computer-based), use of radiation sources (cobalt unit vs. linear accelerator), and fractionation protocols (conventional vs. modified). When the recruitment period of 21 years was divided into 3 intervals, impressive changes with regard to the patterns of care became apparent. However, the changes were seen similarly throughout the different age groups. CONCLUSIONS: Older age did not limit access to state-of-the-art patterns of care in neurooncology. Patients participated in medical progress irrespective of their age. The worse prognosis of older patients with glioblastomas or brain metastases was not determined by age-related differences in access to health care.

Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy: prognostic factors and survival.

AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract. METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively. RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n = 0, stomach: n = 10, colorectal: n = 47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients. WBRT was applied with daily fractions of 2 Gray (Gy) or 3 Gy to a total dose of 50 Gy or 30 Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6 mo vs 8.0 mo for patients with primary tumors of the colon/rectum vs other primary tumors, respectively (P<0.01, log-rank). Median overall survival for all patients with brain metastases (n = 916) was 3.4 mo and 3.2 mo for patients with gastrointestinal neoplasms. Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P<0.05, log-rank). In patients with gastrointestinal neoplasms (n = 57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7 mo for patients with multiple brain metastases (P<0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) >=70 was 5.5 mo vs 2.1 mo for patients with KPS <70 (P<0.01, log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival. CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the number of brain metastases have a profound influence on treatment outcome.

Brain metastases in patients with cancer of unknown primary.

Between January 1985 and December 2000, 916 patients with brain metastases were treated with whole brain radiation therapy (WBRT) at the Department of Radiotherapy, University Hospital Freiburg. In 47 patients, a primary tumor could not be identified (cancer of unknown primary (CUP)). Sixteen patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 15 patients, biopsy alone in 12 patients. WBRT was applied with daily fractions of 2 or 3 Gy to a total dose of 50 or 30 Gy, respectively. According to the recursive partitioning analysis (RPA) classes of the Radiation Therapy Oncology Group for patients with brain metastases none of the patients met the criteria for Class I, 23 for Class II, and 24 for Class III. The median overall survival (OS) for all patients with brain metastases (n = 916) was 3.4 and 4.8 months for patients with CUP (p = 0.45). In patients with CUP (n = 47) the median OS for patients with a single brain metastasis was 7.3 versus 3.9 months for patients with multiple brain metastases (p = 0.05). Median OS for patients with a Karnofsky performance status (KPS) > or = 70 was 6.3 months versus 3.2 months for KPS < 70 (p = 0.01). At multivariate analysis performance status and resection status could be identified as independent prognostic factors for the OS.

Moist skin care can diminish acute radiation-induced skin toxicity.

BACKGROUND: Radiation treatment may induce acute skin reactions. There are several methods of managing them. Validity of these methods, however, is not sufficiently studied. We therefore investigated, whether moist skin care with 3% urea lotion will reduce acute radiation skin toxicity. PATIENTS AND METHODS: 88 patients with carcinomas of the head and neck undergoing radiotherapy with curative intent (mean total dose 60 Gy, range: 50-74 Gy) were evaluated weekly for acute skin reactions according to the RTOG-CTC score. In 63 patients, moist skin care with 3% urea lotion was performed. The control group consisted of 25 patients receiving conventional dry skin care. The incidence of grade I, II, and III reactions and the radiation dose at occurrence of a particular reaction were determined and statistically analyzed using the log-rank test. The dose-time relations of individual skin reactions are described. RESULTS: At some point of time during radiotherapy, all patients suffered from acute skin reactions grade I, > 90% from grade II reactions. 50% of patients receiving moist skin care experienced grade I reactions at 26 Gy as compared to 22 Gy in control patients (p = 0.03). Grade II reactions occurred at 51 Gy versus 34 Gy (p = 0.006). Further, 22% of the patients treated with moist skin care suffered from acute skin toxicity grade III as compared to 56% of the controls (p = 0.0007). CONCLUSION: Moist skin care with 3% urea lotion delays the occurrence and reduces the grade of acute skin reactions in percutaneously irradiated patients with head and neck tumors.

Long-term survival in patients with brain metastases.

PURPOSE: The aims of this study are: (a) to determine long-term survival in patients with brain metastases who underwent whole brain radiation therapy; (b) to evaluate whether long-term survival can be predicted by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA); and (c) to review the literature on long-term survival. MATERIAL AND METHODS: The records of 916 patients with brain metastases who underwent whole brain radiation therapy at our hospital from 1985 to 2000 were analyzed retrospectively. RESULTS: By July 2001, 891 patients had died. Median survival of the whole group was 3.4 months. Overall survival was 5.6% at 2 years (at risk: n=48), 2.9% at 3 years ( n=25), 1.8% at 5 years ( n=12), and <1% at 10 years ( n=1). Survival for 2 years or more was observed in RTOG RPA class 1, but also in class 2 patients. Within both classes, survival was significantly better for patients with a single brain metastasis compared with those patients having multiple metastases. A survey of the literature revealed that in rare instances survival of 10 years or more was seen in patients with brain metastases. The majority of these patients had a single brain metastasis treated by radical resection and whole brain radiation therapy. CONCLUSION: Even in patients with favorable characteristics, survival for 2 years or more after the diagnosis of brain metastases is considerably low. Aggressive therapy in RPA class 1 and class 2 patients with a single brain metastasis occasionally permits long-term survival.

Malignant germ cell tumors metastatic to the brain: a model for a curable neoplasm? The Freiburg experience and a review of the literature.

The aim of this study on malignant germ cell tumors metastasizing to the brain is (a) to report our institutional experience, (b) to present three patients surviving for more than seven years, and (c) to review the literature with regard to long-term survival. From 1985 to 2000, 916 consecutive patients were treated with whole brain radiation therapy for brain metastases at our hospital. Eleven patients had cerebral lesions from histologically proven malignant germ cell tumors. Brain metastases were diagnosed at presentation (n = 2), following complete remission (n = 3), or along with extracerebral tumor progression (n = 6). Seven patients had a single brain metastasis. Three patients underwent resection. Eight patients reached the planned total dose of 50 Gy. Eight patients had chemotherapy. Median survival was 6.6 months. The long-term survivors all had an isolated cerebral relapse after complete remission, presented with a single brain metastasis, and were treated with resection and whole brain radiation therapy to a total dose of 50 Gy. The first patient died from a late relapse 89 months after the diagnosis of brain metastasis, the second patient is well and alive at 95 months. The third patient is currently being treated for a second malignancy originating from the lung. He is alive at 194 months, the longest survival for brain metastases from malignant germ cell tumors ever reported. Altogether, our study demonstrates that advanced extracerebral disease at initial diagnosis and isolated cerebral relapse after complete remission do not preclude long-term survival. Resection and whole brain radiation therapy might result in durable cerebral control with minimal morbidity.

Patients with brain metastases: hope for recursive partitioning analysis (RPA) class 3.

PURPOSE: The objectives of the present study were (a) to validate the prognostic classification derived from recursive partitioning analysis (RPA) of the Radiation Therapy Oncology Group (RTOG); (b) to identify prognostic factors in class 3; (c) to examine the impact of treatment related variables on the prognosis in class 3. PATIENTS AND METHODS: Nine hundred and sixteen patients with brain metastases had resection and whole brain radiotherapy (WBRT, n = 257) or WBRT alone (n = 659) at our institution from 1985 to 2000. Patients were grouped into RPA classes 1, 2, and 3 (n = 67, 441, and 408, respectively). RESULTS: Median survival of the whole group was 3.4 months. Median survival in classes 1, 2, and 3 was 8.2, 4.9, and 1.8 months, respectively. In class 3, age (<65 years vs. > or =65 years, relative risk (RR) 0.75), status of the primary tumor (controlled vs. uncontrolled, RR 0.86), and the number of brain metastases (single vs. multiple, RR 0.76) were independent prognostic variables. We defined three prognostic subgroups: class 3a (n = 51): age <65 years, controlled primary tumor, single brain metastasis; class 3c (n = 44): age > or =65 years, uncontrolled primary tumor, multiple brain metastases; class 3b (n = 313): all other patients. Median survival in classes 3a, 3b, and 3c was 3.2, 1.9, and 1.2 months, respectively (P < 0.0001). Intra-class comparisons showed that resection followed by WBRT yielded significantly better survival compared with WBRT alone. CONCLUSION: Our results validate the RTOG RPA classification for patients with brain metastases. The variables age, status of the primary, and number of brain metastases allow the division of class 3 into prognostic subgroups. Even class 3 patients may benefit from more aggressive treatment strategies.