Treatment of malnutrition decreases complication rates and shortens the length of hospital stays in a radiation oncology department.

PURPOSE: The nutritional status of inpatients influences the therapeutic outcome. Malnutrition is a common comorbidity in oncological patients. Both radio- and radiochemotherapy may contribute to the additional deterioration of the nutritional status. The aim of this study was to evaluate the impact of specialized treatment of malnutrition as a clinical routine. METHODS: The nutritional status of inpatients was assessed by the Nutritional risk screening (NRS-2002) on the day of admission to the University Department of Radiation Oncology. In case of significantly elevated NRS-2002 (NRS ≥ 3), a guideline-compliant, individual nutritional treatment was initiated by a specialized nutrition support team. The influence of the nutritional status and nutritional treatment on length of stay and complication rate was assessed. RESULTS: Of 840 included patients, 344 patients (40.95%) were at risk for malnutrition. Malnutrition was a significant, independent risk factor for both prolonged hospital stay, represented by the deviation between the actual length of stay and the DRG-associated mean length of stay (dLOS at risk: 0.88 days, dLOS not at risk: -0.88 days, p = 0.0047), as well as for the occurrence of complications (OR: 1.758 CI: [1.286-2.402], p = 0.0006). In the group of 337 (40.12%) rehospitalized patients the nutritional management was able to assimilate the values of length of stay as well as the complication rates to standard values. CONCLUSIONS: The high risk for malnutrition and the negative consequences for patients and hospitals underline the urgent need for malnutrition screening on admission and treatment of malnutrition. A specialized, interdisciplinary nutrition support team positively influences patient outcome and should be established routinely in all oncological disciplines.

[Comprehensive nutrition therapy in hospitals - Wishful thinking or reality? A survey-based cross-sectional study of the nutritional therapy in hospitals of Baden-Württemberg]. / Flächendeckende Ernährungstherapie ­ Wunsch oder Wirklichkeit? Eine fragebogengestützte Querschnittsstudie zur ernährungstherapeutischen Versorgung in baden-württembergischen Krankenhäusern.

INTRODUCTION: Malnutrition is widespread in German hospitals, has a negative impact on therapeutic success and quality of life, and it leads to increasing costs. An individualized nutritional support by nutritional professionals in accordance with current guidelines was shown to reduce mortality of malnourished inpatients. Ideally, nutritional support is conducted by an interdisciplinary nutrition support team. Current data on the nutritional therapy in German hospitals is missing. METHODS: In order to ascertain the current status of nutritional support in hospitals in the federal state of Baden-Württemberg, clinic managements of all hospitals in Baden-Württemberg received an online questionnaire. Affiliated hospitals, specialist hospitals, as well as hospitals with less than 50 beds were excluded from the analysis. RESULTS: The response rate was 84% (n = 94). The presence of a nutrition support team was reported by 34% of the hospitals. Twelve percent of the hospitals meet the structural characteristic of the OPS Code 8-98j Ernährungsmedizinische Komplexbehandlung, which means that their nutrition support team includes a physician. A validated nutritional risk screening is performed in 72% of the hospitals. Only 40% of the hospitals report that this is performed throughout every department. Nutrition support teams are more often concerned with malnutrition, enteral and parenteral nutrition as compared to nutritionists who are not organized in a team. Moreover, nutrition support teams have a wider range of tasks and more often a physician as a team member. Also, nutritional risk screenings are more often applied in hospitals with nutrition support teams. DISCUSSION: Compared with a nationwide survey from 2004, there are markedly more nutrition support teams available in hospitals in Baden-Württemberg. When compared internationally, however, the rate of nutrition support teams is still low. In addition, there is no comprehensive nutritional care available. High-quality nutritional support is more often found in hospitals with nutrition support teams. CONCLUSION: There is still a great potential of improving clinical nutritional care in hospitals in Baden-Württemberg. Moreover, an increase in nutrition support teams, also comprising medical members, should be achieved. Therefore, legal regulations and a sufficient refinancing are indispensable.

Prospective evaluation of a hydrogel spacer for rectal separation in dose-escalated intensity-modulated radiotherapy for clinically localized prostate cancer.

BACKGROUND: As dose-escalation in prostate cancer radiotherapy improves cure rates, a major concern is rectal toxicity. We prospectively assessed an innovative approach of hydrogel injection between prostate and rectum to reduce the radiation dose to the rectum and thus side effects in dose-escalated prostate radiotherapy. METHODS: Acute toxicity and planning parameters were prospectively evaluated in patients with T1-2 N0 M0 prostate cancer receiving dose-escalated radiotherapy after injection of a hydrogel spacer. Before and after hydrogel injection, we performed MRI scans for anatomical assessment of rectal separation. Radiotherapy was planned and administered to 78 Gy in 39 fractions. RESULTS: From eleven patients scheduled for spacer injection the procedure could be performed in ten. In one patient hydrodissection of the Denonvillier space was not possible. Radiation treatment planning showed low rectal doses despite dose-escalation to the target. In accordance with this, acute rectal toxicity was mild without grade 2 events and there was complete resolution within four to twelve weeks. CONCLUSIONS: This prospective study suggests that hydrogel injection is feasible and may prevent rectal toxicity in dose-escalated radiotherapy of prostate cancer. Further evaluation is necessary including the definition of patients who might benefit from this approach. TRIAL REGISTRATION: German Clinical Trials Register DRKS00003273.

Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: The HEAT randomised clinical trial.

BACKGROUND: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pre-treated patients with advanced pancreatic ductal adenocarcinoma. We conducted a randomised clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected pancreatic ductal adenocarcinoma. METHODS: This randomised, multicentre, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m2 on day 1, 15 and cisplatin 25 mg/m2 with RHT on day 2, 3 and 15,16) or to G (gemcitabine 1000 mg/m2 on day 1,8,15), four-weekly over six cycles. Disease-free survival (DFS) was the primary end-point. Secondary end-points included overall survival (OS) and safety. RESULTS: A total of 117 eligible patients (median age, 63 years) were randomly allocated to treatment (57 GPH; 60 G). With a follow-up time of 56.6 months, the median DFS was 12.7 compared to 11.2 months for GPH and G, respectively (p = 0.394). Median post-recurrence survival was significantly prolonged in the GPH-group (15.3 versus 9.8 months; p = 0.031). Median OS reached 33.2 versus 25.2 months (p = 0.099) with 5-year survival rates of 28.4% versus 18.7%. Excluding eight patients who received additional capecitabine in the G-arm (investigators choice), median OS favoured GPH (p = 0.052). Adverse events CTCAE (Common Terminology Criteria for Adverse Events) grade ≥3 occurred in 61.5% (GPH) versus 63.6% (G) of patients. Two patients in the G-group died because of treatment-related toxic effects. CONCLUSIONS: The randomised controlled Hyperthermia European Adjuvant Trial study failed to demonstrate a significant difference in DFS. However, it suggests a difference in post-recurrence survival and a trend for improved OS. CLINICALTRIALS: gov, number NCT01077427.

NOA-05 phase 2 trial of procarbazine and lomustine therapy in gliomatosis cerebri.

OBJECTIVE: The NOA-05 multicenter trial was performed to analyze the efficacy of primary chemotherapy with procarbazine and lomustine (PC) in patients with gliomatosis cerebri (GC) and to define clinical, imaging, and molecular factors influencing outcome. METHODS: Thirty-five patients with previously untreated GC were treated with up to six 56-day courses of 110mg/m(2) lomustine on day 1 and 60mg/m(2) procarbazine on days 8 to 21. The primary endpoint was the rate of patients without therapy failure (defined as progressive disease, death from any cause, or termination of PC therapy before the end of course 4) at 8 months after the beginning of PC chemotherapy. RESULTS: The failure-free survival rate at 8 months was 50.3%. Median progression-free survival was 14 months. At progression, 12 patients received salvage radiotherapy. Median overall survival was 30 months. Multivariate analysis revealed isocitrate dehydrogenase 1 (IDH1) gene mutation (hazard ratio [HR], 0.11; 95% confidence interval [CI], 0.02-0.58) and initial presentation without a bilateral symmetrical infiltration pattern on magnetic resonance imaging (HR 0.07, 95%CI 0.01-0.54) as independent prognostic factors associated with prolonged survival. IDH1 mutation was significantly associated with MGMT promoter methylation and an oligodendroglial tumor component. INTERPRETATION: PC chemotherapy is effective in GC. With the NOA-05 trial being the first prospective multicenter trial in GC, PC chemotherapy can be regarded as a promising option for the primary therapy of these tumors.

Pathological complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with regional hyperthermia for locally advanced rectal cancer compared with radiochemotherapy alone.

PURPOSE: To evaluate the influence of regional hyperthermia on rates of complete pathological response (pCR) and sphincter-sparing surgery in the context of an up-to-date radiochemotherapy protocol for locally advanced rectal cancer. METHODS: Between 2007 and 2010, 106 patients with locally advanced cancer of the middle and lower rectum were admitted to neoadjuvant radiochemotherapy either with (n = 61) or without (n = 45) regional hyperthermia. A retrospective comparison was performed between two groups: 45 patients received standard treatment consisting of 5040 cGy in 28 fractions to the pelvis and 5-fluorouracil (RCT group) and 61 patients received the same treatment in combination with regional hyperthermia (HRCT group). Target temperature was 40.5°C for at least 60 min. Total mesorectal excision was performed routinely. RESULTS: pCR was seen in 6.7% of patients in the RCT group and 16.4% in the HRCT group. Patients who received at least four hyperthermia treatments (n = 40) achieved a significantly higher pCR rate (22.5%) than the remaining 66 patients (p = 0.043). Rates of sphincter-sparing surgery were similar in both groups with 64% in the RCT group and 66% in HRCT. When considering only low-lying tumours located within 8 cm of the anal verge prior to treatment, the rate of sphincter-sparing surgery was 57% in the HRCT group compared with 35% in the RCT group (p = 0.077). CONCLUSION: The combination of regional hyperthermia and neoadjuvant radiochemotherapy may lead to an increased pCR rate in locally advanced rectal cancer. Patients with low-lying tumours especially may benefit when additional downsizing allows sphincter-preserving surgery.

New shift models for doctors in a large German University Neurosurgery Department: how they comply with the European Working Time Directive 3 years after implementation.

BACKGROUND: Due to the European Working Time Directive (EWTD) and a new collective agreement for doctors working at University hospitals in 2006 new shift models had to be designed in the Department of Neurosurgery of the University Hospital Tübingen, Germany. The aim of the study was to show the fit of the models regarding the average weekly working time limits (aWTL), the daily maximum of 10-h working time (10-h dWT), and the staff expenditures 3 years after implementation. METHODS: The new shift model was implemented in 2008, and hence planning and documentation were done electronically. Adherence to the work schedules was measured, and aWTL adherence rates were compared. The relative number of 10-h dWT violations in 2009 and 2010 was analysed. Staff costs relative to performance before and after implementation were calculated and tested using analysis of variance (ANOVA). Four other departments without alteration of shift models served as a control group in cost trend analysis. RESULTS: In 2010 all doctors in the Department of Neurosurgery were able to stay within the limit of 54 h/week; one doctor without opt-out exceeded the 48 h/week limit (50.1 h/week). The median per capita rate of 10-h dWT violations in 2009 was 20.3 % of all eligible working days and further declined to 10.7 % in 2010 (p < 0.001). Staff costs per case-weight point did not change significantly (2007: 339.88€, 2009: 307.99€, 2010: 322.54€; p = 0.22) in neurosurgery or in the control group (2007: 633.72€, 2009: 637.06€, 2010: 690.30€; p = 0.67). CONCLUSIONS: After implementation of the new shift model, current monitoring and properly matching modifications led to long-term stability in complying with the EWTD regulations without increasing costs for staff expenditures.

Optimizing the quality of breast cancer care at certified german breast centers: a benchmarking analysis for 2003-2009 with a particular focus on the interdisciplinary specialty of radiation oncology.

PURPOSE: A voluntary, external, science-based benchmarking program was established in Germany in 2003 to analyze and improve the quality of breast cancer (BC) care. Based on recent data from 2009, we aim to show that such analyses can also be performed for individual interdisciplinary specialties, such as radiation oncology (RO). METHODS: Breast centers were invited to participate in the benchmarking program. Nine guideline-based quality indicators (QIs) were initially defined, reviewed annually, and modified, expanded, or abandoned accordingly. QI changes over time were analyzed descriptively, with particular emphasis on relevance to radiation oncology. RESULTS: During the 2003-2009 study period, there were marked increases in breast center participation and postoperatively confirmed primary BCs. Starting from 9 process QIs, 15 QIs were developed by 2009 as surrogate indicators of long-term outcome. During 2003-2009, 2/7 RO-relevant QIs (radiotherapy after breast-conserving surgery or after mastectomy) showed considerable increases (from 20 to 85% and 8 to 70%, respectively). Another three, initially high QIs practically reached the required levels. CONCLUSION: The current data confirm proof-of-concept for the established benchmarking program, which allows participating institutions to be compared and changes in quality of BC care to be tracked over time. Overall, marked QI increases suggest that BC care in Germany improved from 2003-2009. Moreover, it has become possible for the first time to demonstrate improvements in the quality of BC care longitudinally for individual breast centers. In addition, subgroups of relevant QIs can be used to demonstrate the progress achieved, but also the need for further improvement, in specific interdisciplinary specialties.

Comparison of different adjuvant radiotherapy approaches in childhood bladder/prostate rhabdomyosarcoma treated with conservative surgery.

BACKGROUND AND PURPOSE: Multimodality treatment approaches provide high local control and satisfying overall survival (OS) for children with localized bladder and/or prostate rhabdomyosarcoma (BP-RMS). However, current strategies including surgery and conventional radiotherapy are compromised by high rates of long-term genitourinary adverse effects. Therefore, a planning study combining organ preserving surgery with three different innovative adjuvant radiotherapy approaches was performed. PATIENTS AND METHODS: A case of a 21-month-old boy with BP-RMS treated with polychemotherapy according to the CWS 2002-P protocol, prostatectomy, partial cystectomy, and adjuvant high dose rate brachytherapy (HDR-BT) was used to perform a planning study comparing HDR-BT with intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) planning. RESULTS: All modalities provide good coverage of the target volume and spare critical normal tissues. Rectum doses could be reduced by 2/3 using IMPT and by 1/3 using BT compared to IMRT. In terms of sparing the pelvis growth plates, BT and IMPT are also superior to IMRT. CONCLUSION: All modalities provide good sparing of normal tissue. BT and IMPT are superior to IMRT with regard to doses on rectum and growth plates. BT is equivalent to IMPT in adequately selected tumors.

Impact of radiotherapy, chemotherapy and surgery in multimodal treatment of locally advanced esophageal cancer.

OBJECTIVES: It was the aim of this study to assess our institutional experience with definitive chemoradiation (CRT) versus induction chemotherapy followed by CRT with or without surgery (C-CRT/S) in esophageal cancer. METHODS: We retrospectively analyzed 129 institutional patients with locally advanced esophageal cancer who had been treated by either CRT in analogy to the RTOG 8501 trial (n = 78) or C-CRT/S (n = 51). RESULTS: The median, 2- and 5-year overall survival (OS) of the entire collective was 17.6 months, 42 and 24%, respectively, without a significant difference between the CRT and C-CRT/S groups. In C-CRT/S patients, surgery statistically improved the locoregional control (LRC) rates (2-year LRC 73.6 vs. 21.2%; p = 0.003); however, this was translated only into a trend towards improved OS (p = 0.084). The impact of escalated radiation doses (≥60.0 vs. <60.0 Gy) on LRC was detectable only in T1-3 N0-1 M0 patients of the CRT group (2-year LRC 77.8 vs. 42.3%; p = 0.036). CONCLUSION: Definitive CRT and a trimodality approach including surgery (C-CRT/S) had a comparable outcome in this unselected patient collective. Surgery and higher radiation doses improve LRC rates in subgroups of patients, respectively, but without effect on OS.

Re-surgery and chest wall re-irradiation for recurrent breast cancer: a second curative approach.

BACKGROUND: Repeat radiation is a rarely used treatment strategy that must be performed with caution. The efficacy and toxicity of a second curative radiotherapy series was investigated in cases of recurrent breast cancer. METHODS: Forty-two patients treated from 1993 to 2003 with resection (n = 30) and postoperative re-irradiation or definitive re-irradiation (n = 12) for recurrent breast cancer were enrolled in the study. Concurrent hyperthermia was performed in 29 patients. The median age was 57 years. The median pre-radiation exposure was 54Gy. Re-irradiation was conventionally fractionated to a median total dose of 60Gy. RESULTS: After a median follow-up of 41 months (range 3-92 months) higher graded late toxicity > G3 according to CTC 3.0 and LENT-SOMA was not observed. The estimated 5-year local control rate reached 62%. The estimated 5-year overall survival rate was 59%. Significantly inferior survival was associated with recurrence within two years (40 vs. 71%, p < ([0-9]).01) and presence of macroscopic tumour load (24 vs. 75%, p = 0.03). CONCLUSIONS: Repeat radiotherapy for recurrent breast cancer with total radiation doses of 60 Gy and the addition of hyperthermia in the majority of patients was feasible, with acceptable late morbidity and improved prognosis, particularly in patients with previous resection of recurrent tumours.

High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial.

BACKGROUND: High-dose methotrexate is the standard of care for patients with newly diagnosed primary CNS lymphoma. The role of whole brain radiotherapy is controversial because delayed neurotoxicity limits its acceptance as a standard of care. We aimed to investigate whether first-line chemotherapy based on high-dose methotrexate was non-inferior to the same chemotherapy regimen followed by whole brain radiotherapy for overall survival. METHODS: Immunocompetent patients with newly diagnosed primary CNS lymphoma were enrolled from 75 centres and treated between May, 2000, and May, 2009. Patients were allocated by computer-generated block randomisation to receive first-line chemotherapy based on high-dose methotrexate with or without subsequent whole brain radiotherapy, with stratification by age (<60 vs ≥60 years) and institution (Berlin vs Tübingen vs all other sites). The biostatistics centre assigned patients to treatment groups and informed local centres by fax; physicians and patients were not masked to treatment group after assignment. Patients enrolled between May, 2000, and August, 2006, received high-dose methotrexate (4 g/m(2)) on day 1 of six 14-day cycles; thereafter, patients received high-dose methotrexate plus ifosfamide (1·5 g/m(2)) on days 3-5 of six 14-day cycles. In those assigned to receive first-line chemotherapy followed by radiotherapy, whole brain radiotherapy was given to a total dose of 45 Gy, in 30 fractions of 1·5 Gy given daily on weekdays. Patients allocated to first-line chemotherapy without whole brain radiotherapy who had not achieved complete response were given high-dose cytarabine. The primary endpoint was overall survival, and analysis was per protocol. Our hypothesis was that the omission of whole brain radiotherapy does not compromise overall survival, with a non-inferiority margin of 0·9. This trial is registered with ClinicalTrials.gov, number NCT00153530. FINDINGS: 551 patients (median age 63 years, IQR 55-69) were enrolled and randomised, of whom 318 were treated per protocol. In the per-protocol population, median overall survival was 32·4 months (95% CI 25·8-39·0) in patients receiving whole brain radiotherapy (n=154), and 37·1 months (27·5-46·7) in those not receiving whole brain radiotherapy (n=164), hazard ratio 1·06 (95% CI 0·80-1·40; p=0·71). Thus our primary hypothesis was not proven. Median progression-free survival was 18·3 months (95% CI 11·6-25·0) in patients receiving whole brain radiotherapy, and 11·9 months (7·3-16·5; p=0·14) in those not receiving whole brain radiotherapy. Treatment-related neurotoxicity in patients with sustained complete response was more common in patients receiving whole brain radiotherapy (22/45, 49% by clinical assessment; 35/49, 71% by neuroradiology) than in those who did not (9/34, 26%; 16/35, 46%). INTERPRETATION: No significant difference in overall survival was recorded when whole brain radiotherapy was omitted from first-line chemotherapy in patients with newly diagnosed primary CNS lymphoma, but our primary hypothesis was not proven. The progression-free survival benefit afforded by whole brain radiotherapy has to be weighed against the increased risk of neurotoxicity in long-term survivors.

Radiation protection of persons living close to patients with radioactive implants.

BACKGROUND: Permanent interstitial brachytherapy is--in certain cases--a very successful therapeutic option, but application of radioactive implants always results in only gradually diminishing radiation exposure of persons in the patient's immediate surroundings. MATERIAL AND METHODS: Using patients with clinically localized prostate cancer treated with iodine-125 ((125)I) or palladium-103 ((103)Pd) as an example, it is shown how a patient, if necessary or wished by him, can, by wearing commercially available X-ray protection shorts, reduce radiation exposure of family members in such a way that at a distance r from the patient a given dose per year is not exceeded. RESULTS: The computational procedures necessary for the determination of the individual periods of wearing X-ray protection clothing are provided in the form of formulae and graphics. All considerations and calculations can also be applied to other radiotherapeutic interventions involving the use of (125)I, (103)Pd or other gamma-sources. CONCLUSION: If necessary, a patient with permanent radioactive implants can reduce radiation exposure of family members by wearing special X-ray protection clothing for a limited period of time. This kind of radiation protection is very efficient and considerably simpler to accomplish than a reduction of exposure time or an increase of the distance between the patient and family members.

Small cell carcinoma of vulva: curative multimodal treatment in face of resistance to initial standard chemotherapy.

BACKGROUND AND PURPOSE: Extrapulmonary small cell carcinoma (EPSCC) is a rare disease, which has a slightly better prognosis than small cell lung cancer, but still dismal. Gynecologic small cell malignancies tend to show a better survival than similar histologies of other regions. However, of five reported cases of vulvar manifestation only one patient was disease-free at the time of publication with limited follow-up. CASE REPORT: The authors describe a case of locally advanced small cell vulva carcinoma infiltrating the anal sphincter and urethra with spread to inguinal lymph nodes treated by radiochemotherapy and regional hyperthermia. After three cycles of carboplatin/ etoposide, computed tomography and magnetic resonance imaging indicated only little regressive transformations but overall stable disease. Surgical options were excluded. Therefore, curative radiotherapy to a total dose of > 65 Gy to macroscopic tumor, chemotherapy with cisplatin weekly, and regional hyperthermia were performed. Acute severe toxicity was limited to skin reactions. Despite the disadvantageous situation with inguinal lymph node metastases and chemoresistance, the multimodal therapy yielded a 5-year disease-free survival. CONCLUSION: Thus, the trimodal regimen of radiochemotherapy plus regional hyperthermia offered a curative chance in spite of resistance to the standard chemotherapy for irresectable, locally advanced small cell carcinoma of the vulva. Therefore, this approach merits further evaluation for limited disease of EPSCC.

Nodal follicular lymphoma: the role of radiotherapy for stages I and II.

PURPOSE: To clarify the role of external-beam radiotherapy (RT) in patients with stage I and II nodal follicular lymphoma (FL). METHODS: The literature was reviewed with respect to different treatment strategies in patients with stage I and II nodal FL by screening the PubMed databank. RESULTS: In patients with stage I and II nodal FL, RT alone with different irradiation techniques (involved-field [IFI]/extended-field [EFI]/total nodal [TNI]/total lymphoid irradiation [TLI]) produces excellent local disease control (approximately 95%) resulting in disease-free survival and overall survival (OS) rates of 37-94% and 40-93% at 5-15 years, respectively. The main cause of failure is out-of-field recurrence. In nonrandomized trials, IFI led to higher relapse rates, but larger irradiation volumes failed to show an impact on OS and were associated with increased toxicity. Additional chemotherapy mostly failed to improve treatment results achieved with RT alone. CONCLUSION: Since there is no evidence so far that the prognosis of stage I and II nodal FL can be improved by the use of EFI/TNI/TLI, IFI is recommended internationally. Adequate irradiation doses range between 25-30 Gy to subclinical disease and 36-40 Gy to involved sites. To further improve the curative potential of RT in early-stage FL, novel combined approaches (e.g., RT + immunotherapy with rituximab) are under investigation.

Fibrotic changes after postmastectomy radiotherapy and reconstructive surgery in breast cancer. A retrospective analysis in 109 patients.

PURPOSE: The purpose of this study was to analyze the probability and time course of fibrotic changes in breast reconstruction before or after postmastectomy radiotherapy (PMRT). MATERIALS AND METHODS: Between 1995 and 2004, 109 patients were treated with PMRT at Tübingen University and underwent heterologous (HL) or autologous (AL) breast reconstruction prior or subsequent to radiation therapy. Fibrosis of the reconstructed breast after radiotherapy was assessed using the Baker score for HL reconstructions and the Common Terminology Criteria for Adverse Events (CTCAE) for all patients. Actuarial rates of fibrosis were calculated for the maximum degree acquired during follow- up and at the last follow-up visit documented. RESULTS: Median time to follow-up was 34 months (3-227 months). Radiotherapy was applied with a median total dose of 50.4 Gy. A total of 44 patients (40.4%) received a boost treatment with a median dose of 10 Gy. Breast reconstruction was performed with AL, HL, or combined techniques in 20, 82, and 7 patients, respectively. The 3-year incidence of ≥ grade III maximum fibrosis was 20% and 43% for Baker and CTCAE scores, respectively. The corresponding figures for fibrosis at last follow-up visit were 18% and 2%. The 3-year rate of surgical correction of the contralateral breast was 30%. Initially unplanned surgery of the reconstructed breast was performed in 39 patients (35.8%). Boost treatment and type of cosmetic surgery (HL vs. AL) were not significantly associated with the incidence of fibrosis. CONCLUSIONS: We found severe fibrosis to be a frequent complication after PMRT radiotherapy and breast reconstruction. However, surgical intervention can ameliorate the majority of high grade fibrotic events leading to acceptable long-term results. No treatment parameters associated with the rate of fibrosis could be identified.

Advanced-stage III/IV follicular lymphoma: treatment strategies for individual patients.

BACKGROUND: In patients with advanced-stage III/IV follicular lymphoma (FL), there are many treatment options available. The current challenge is to choose the optimal strategy for the individual patient. METHODS: The literature was reviewed with respect to treatment strategies in patients with advanced FL by screening the PubMed databank. RESULTS: In advanced-stage III/IV FL, median survival may approach 8-10 years. Treatment strategies include a watch-and-wait strategy, chemoimmunotherapy, monotherapy with rituximab, and - as an experimental approach so far - radioimmunotherapy. The use of autologous hematopoietic stem cell transplantation (HSCT) for patients in first remission or chemosensitive relapse prolongs progression-free survival while the effect on overall survival remains unclear compared to standard chemotherapy. However, long-term results are flawed by high relapse rates and risk of secondary malignancies. In patients with relapsed/chemoresistant disease, allogeneic HSCT constitutes the only curative approach but is associated with high treatment-related mortality. In the palliative setting, low-dose involved-field irradiation constitutes an effective treatment option in order to control local symptoms with potential long-lasting response. CONCLUSION: In case of advanced-disease FL, asymptomatic patients can be managed expectantly. In symptomatic patients, chemoimmunotherapy is regarded as standard therapy. In symptomatic elderly patients with relevant comorbidities, rituximab +/- single-agent chemotherapy, or low-dose involved-field radiotherapy might be appropriate. For younger patients with chemoresistant/relapsed disease, allogeneic HSCT might be considered, since advances in supportive care and better patient selection have resulted in improved outcomes.

Reirradiation with alternating docetaxel-based chemotherapy for recurrent head and neck squamous cell carcinoma: update of a single-center prospective phase II protocol.

PURPOSE: To report follow-up data and results of a dose escalation within a prospective phase II protocol scheduling alternating chemoreirradiation for patients with unresectable locoregional recurrence of head and neck cancer after previous curative-intent radiotherapy. PATIENTS AND METHODS: Chemoreirradiation was initially performed in 27 patients by 40.0 Gy split-course reirradiation (re-RT) alternating with three cycles of docetaxel 50 mg/m(2) day 1 and cisplatin 15 mg/m(2) days 2-5 (first cohort). From 2002 onward, 30 consecutively treated patients received a late-course concomitant boost to 49.6 Gy (second cohort). In July 2008, the survival outcome was analyzed separately for both cohorts and the entire collective (n = 57). RESULTS: The Kaplan-Meier estimates for 1- and 2-year overall survival (OS) were 52% and 24%, respectively (median OS 13.4 months). The median time of locoregional control was 9.6 months, and the actuarial 2-year freedom from distant metastasis rate was 55%. The re-RT dose escalation led to a significant improvement of the median OS (17.4 vs. 9.4 months; p = 0.039). Irrespective of the cohort, severe treatment-related toxicities occurred in about one third of patients. CONCLUSION: The treatment results confirm the efficacy and the safety of escalated re-RT doses in this chemoreirradiation protocol.

Superiority of temozolomide over radiotherapy for elderly patients with RTK II methylation class, MGMT promoter methylated malignant astrocytoma.

BACKGROUND: O6-methylguanine DNA-methyl transferase (MGMT) promoter methylation status is predictive for alkylating chemotherapy, but there are non-benefiting subgroups. METHODS: This is the long-term update of NOA-08 (NCT01502241), which compared efficacy and safety of radiotherapy (RT, n = 176) and temozolomide (TMZ, n = 193) at 7/14 days in patients >65 years old with anaplastic astrocytoma or glioblastoma. DNA methylation patterns and copy number variations were assessed in the biomarker cohort of 104 patients and in an independent cohort of 188 patients treated with RT+TMZ-containing regimens in Heidelberg. RESULTS: In the full NOA-08 cohort, median overall survival (OS) was 8.2 [7.0-10.0] months for TMZ treatment versus 9.4 [8.1-10.4] months for RT; hazard ratio (HR) = 0.93 (95% CI: 0.76-1.15) of TMZ versus RT. Median event-free survival (EFS) [3.4 (3.2-4.1) months vs 4.6 (4.2-5.0) months] did not differ, with HR = 1.02 (0.83-1.25). Patients with MGMT methylated tumors had markedly longer OS and EFS when treated with TMZ (18.4 [13.9-24.4] mo and 8.5 [6.9-13.3] mo) versus RT (9.6 [6.4-13.7] mo and 4.8 [4.3-6.2] mo, HR 0.44 [0.27-0.70], P < 0.001 for OS and 0.46 [0.29-0.73], P = 0.001 for EFS). Patients with glioblastomas of the methylation classes receptor tyrosine kinase I (RTK I) and mesenchymal subgroups lacked a prognostic impact of MGMT in both cohorts. CONCLUSION: MGMT promoter methylation is a strong predictive biomarker for the choice between RT and TMZ. It indicates favorable long-term outcome with initial TMZ monotherapy in patients with MGMT promoter-methylated tumors primarily in the RTK II subgroup.

Hypofractionated reirradiation for recurrent malignant glioma.

BACKGROUND AND PURPOSE: Treatment options for recurrent high-grade glioma after a complete course of radiotherapy comprise surgery, reirradiation and chemotherapy but the efficacy of any of the given salvage treatments is limited. In order to further define the role of short-term radiotherapy as retreatment option for selected patients, we analyzed outcomes after treatment with a hypofractionated radiation. PATIENTS AND METHODS: Treatment outcomes (overall survival and treatment-associated toxicity) were analyzed retrospectively in 31 patients treated between 1994 and 2007. Hypofractionated radiotherapy was performed after three-dimensional CT planning with a median total dose of 20 Gy in a single department. RESULTS: With a median interval of 20 months from primary radiotherapy, two grade III and 29 grade IV tumors were reirradiated. Pretreatment consisted of surgery and involved-field radiotherapy (median 59 Gy). 77% of the patients received additional chemotherapy before the second course of radiotherapy, and 48% were treated after secondary resection. The median overall survival after hypofractionated radiotherapy was 10.2 months, and the median overall survival time after primary diagnosis 30.9 months. No severe toxicity was observed. CONCLUSION: Hypofractionated reirradiation with 20 Gy given over 1 week is a practicable and well-tolerated treatment option for patients with recurrent malignant glioma. The overall survival was comparable to the reported outcomes from other series including those with longer treatment protocols.