Radiation therapy of breast cancer in the Nahe Breast Center: first results of an analysis in the context of health services research.

BACKGROUND: The first evaluation of radiotherapy results in patients with breast cancer treated as part of a multimodal oncologic therapy in the Nahe Breast Center is presented. Analysis of the results was performed using an in-practice registry. PATIENTS AND METHODS: From September 2016 to December 2017, 138 patients (median age 62.5 years; range 36-94 years) with breast cancer (right side, n = 67; left side, n = 71) received adjuvant radiation therapy. Of these, 103 patients received gyneco-oncologic care at the Nahe Breast Center, and 35 were referred from outside breast centers. The distribution into stages was as follows: stage I, n = 48; stage II, n = 68; stage III, n = 19; stage IV, n = 3. Neoadjuvant chemotherapy was given to 19 and adjuvant chemotherapy to 50 patients. Endocrine treatment was given to 120 patients. Both 3D conformal (n = 103) and intensity-modulated (n = 35) radiotherapy were performed with a modern linear accelerator. RESULTS: With a median follow-up of 60 months (1-67), local recurrence occurred in 4/138 (2.9%) and distant metastasis in 8/138 (5.8%) patients; 7/138 (5.1%) patients died of their tumors during the follow-up period. The actuarial 5­year local recurrence-free survival of all patients was 97.1%, and the actuarial 5­year overall survival of all patients was 94.9%. We observed no grade 3 or 4 radiogenic side effects. CONCLUSION: The results of radiotherapy for breast carcinoma at the Nahe Breast Center are comparable to published national and international results. In particular, the local recurrence rates in our study, determined absolutely and actuarially, are excellent, and demonstrate the usefulness of radiotherapy.

DEGRO guidelines for the radiotherapy of non-malignant disorders : part III: hyperproliferative disorders.

BACKGROUND AND PURPOSE: Radiation therapy (RT) is an established and effective treatment modality in the management of a large variety of hyperproliferative disorders and benign neoplasms. Objective of this article is to summarize the updated DEGRO consensus S2e guideline recommendations. MATERIALS AND METHODS: This report comprises an overview of the relevant aspects of the updated guidelines with regard to treatment decision, dose prescription, and RT technique for a selected group of disorders including Morbus Dupuytren (MD)/Morbus Ledderhose (ML), keloids, Peyronie's disease (induratio penis plastica, IPP), desmoid tumors, pigmented villonodular synovitis (PVNS), symptomatic vertebral hemangiomas (sVH), and Gorham-Stout syndrome (GSS). On the basis of results in the literature, we attempted to classify the level of evidence (LoE) and the grade of recommendation (GR) according to the Oxford criteria. RESULTS: There is comprehensive evidence in the literature that RT is a reasonable and effective treatment modality for the treatment of all the above-mentioned disorders. The LoE varies from 2c to 4, and GR varies from A to C. CONCLUSIONS: The use of RT can be recommended for the interdisciplinary management of most of the reported disorders. It can be used in the primary treatment approach and as an effective adjunct to other treatment modalities or in some indications as a valuable alternative treatment option. We hope that the updated DEGRO S2e consensus guideline recommendations are a helpful tool for radiation oncologists in the clinical decision-making process.

[Micronutrients in oncology. Current data about vitamin D, selenium, L-carnitine and vitamin C]. / Mikronährstoffe in der Onkologie. Aktuelles zu Vitamin D, Selen, L-Carnitin und Vitamin C.

Many patients receiving cancer treatment use micronutrient supplements, with the intention to complement their cancer treatment, or help them cope with the therapy- and disease-associated side-effects. Up to 90% of the cancer patients are adding antioxidants without the knowledge of the treating physician. There are many concerns that antioxidants might decrease the effectiveness of chemotherapy, but increasing evidence suggests a benefit when antioxidants and other micronutrients, such as selenium, L-carnitine and vitamin D are added to conventional cytotoxic therapies. It is imperative that physicians discuss the use ofantioxidant and other micronutrient supplements with their cancer patients and educate them about potentially negative, but also potentially beneficial effects.

[Essential trace elements, vitamins, and selected electrolytes in complementary medicine for cancer patients]. / Essentielle Spurenelemente, Vitamine und ausgewählte Elektrolyte in der Komplementärmedizin für Tumorpatienten.

OBJECTIVE: Are there any evidence-based medicine (EBM)-supported treatment approaches of complementary and alternative medicine (CAM) methods for urological oncologists? METHODS: We reviewed the actual German S3 guidelines "Supportive Care" and "Complementary Medicine" as well as the online-tool Onkopedia for recommendations about essential trace elements (Zn, Se, Mn, Fe), vitamins (A, B, C, D, E), and electrolytes (Mg, Ca). Furthermore, we added results of randomized trials to present potential future developments. RESULTS: Each therapy with micronutrients should be based on laboratory observation of a deficit. There are selected guideline recommendations for selenium, iron and vitamin D. Potential indications were registered for manganese, vitamin A derivates, and vitamin C. No benefit was observed for vitamin B, zinc, and vitamin E. CONCLUSION: Micronutrients should be substituted in the case of deficit. General supplementation of daily nutrition is not recommended for cancer patients.

Radiotherapy of splenomegaly : a palliative treatment option for a benign phenomenon in malignant diseases.

PURPOSE: Since the 20(th) century, radiotherapy (RT) has been used for treatment of symptomatic splenomegaly (SM). SM occurs in association with hematologic disorders. The purpose of this analysis was to determine the indication, treatment concepts, and efficiency of RT. MATERIAL AND METHODS: Clinical features, treatment concepts, and outcome data during the past 20 years were analyzed. Endpoints were pain relief, symptomatic and hematological response, and treatment-related side effects. RESULTS: From 1989-2009, a total of 122 patients received 246 RT courses because of symptomatic SM. Overall 31 patients had chronic myelogenous leukemia (CML), 37 had chronic lymphocytic leukemia (CLL), 23 had osteomyelofibrosis (OMF), 17 had polycythemia vera (PV), 5 had acute myelogenous leukemia, 4 had idiopathic thrombocytopenic purpura (ITP), 3 had non-Hodgkin lymphoma (NHL), and 2 had multiple myeloma (MM). Patients were treated with (60)Co gamma rays or 5-15MV photons. The fraction size ranged from 10-200 cGy and the total dose per treatment course from 30-1600 cGy. Significant pain relief was achieved for 74.8% of the RT courses given for splenic pain. At least 50% regression was attained for 77% of the RT courses given for SM. 36 patients died within 2 months due to the terminal nature of their disease. Of the RT courses applied for cytopenia, 73.6% achieved a significant improvement of hematological parameters and reduction of transfusion need. Notable hematologic toxicities were reported < EORTC/RTOG II°. CONCLUSION: The present analysis documents the efficacy of RT. In addition, RT as a palliative treatment option for symptomatic SM should not be forgotten.

[Complementary medicine in uro-oncology]. / Komplementärmedizin in der Uroonkologie.

Complementary and alternative medicine (CAM) is widespread in oncology patients with a user rate of approximately 40-50%. An accompanying supportive effect can arise through improved adherence, especially in long-term (e.g. endocrine) therapies through active patient involvement. When assessing the evidence on frequently requested methods, there is no high-quality evidence that homeopathy or anthroposophy leads to an improved prognosis. Mistletoe therapy can be considered to improve the quality of life, although the data quality is weak. In prostate cancer, pomegranate has an influence on the prostate-specific antigen. It is currently unclear whether this will also result in an improved prognosis. In contrast the evidence on selenium and vitamin D speaks in favor of integration into the aftercare concept. Supplementation is recommended after the serum level has been determined.

[Radiotherapy in painful gonarthrosis. Results of a national patterns-of-care study]. / Strahlentherapie bei schmerzhafter Kniegelenkarthrose (Gonarthrose): Ergebnisse einer deutschen Patterns-of-Care-Studie

BACKGROUND AND PURPOSE: After a patterns-of-care study (PCS) in 2003/2004 addressing benign disorders in general, the German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD) conducted several multicenter cohort studies including the use of radiotherapy (RT) in painful gonarthrosis (GNA). MATERIAL AND METHODS: From 2006 to 2008, a PCS for GNA was conducted in all German RT institutions using a standardized structured questionnaire. Patient accrual, patient number, pretreatment, pain record, treatment indications, RT technique, and target volume concepts for painful GNA were assessed. In addition, the long-term functional and subjective outcomes were evaluated. RESULTS: 238/248 institutions (95.9%) returned the questionnaire: 50 (21%) reported no clinical experience with RT in GNA, while 188 (79%) institutions treated 4,544 patients annually (median 15; range one to 846 cases per institution). Indications for treatment were acute pain symptoms in 18.9%, chronic pain in 95.3%, and treatment-refractory pain in 81.1%. The median total dose was 6 Gy (range 3-12 Gy), with a median single dose of 1 Gy (0.25-3 Gy). 40.4% of the institutions applied two fractions and 51.4% three fractions weekly. RT was delivered with orthovoltage units (25%), linear accelerators (79.6%), and cobalt-60 units (8.3%). 42 institutions evaluated the long-term clinical outcome in a total of 5,069 cases. Median pain reduction for at least 3 months was reported in 60% (5-100%), median pain reduction for at least 12 months in 40% (10-100%), and median persistent pain reduction in 27.8% (10-85%) of the treated patients. In 30% of patients (7-100%), a second RT series was applied for inadequate pain response or early pain recurrence. No radiogenic acute or chronic side effects were observed. CONCLUSION: This PCS comprises the largest number of cases reported for RT in painful and refractory GNA. Despite variations in daily RT practice, high response and low toxicity for this treatment in a very large number of painful and refractory GNA cases renders low-dose RT an effective conservative therapy which can be applied prior to surgical procedures.

Malnutrition and Survival - Bioimpedance Data in Head Neck Cancer Patients.

BACKGROUND/AIM: Bioimpedance analysis (BIA) reflects the nutritional status of patients. The aim of this study was to examine whether BIA is able to document the possible impact of malnutrition on survival. MATERIALS AND METHODS: The registered data of 42 head and neck cancer patients were analyzed. Survival data of 22 women and 20 men were included. The mean age was 67.3±10.77 years. BIA was measured by the Biocorpus 4000 RX (MEDIcal Health Care GmbH Karlsruhe) and summarized in individual phase angle (PA) of each patient. RESULTS: Patients with normal PA>5.0 had a significantly better survival (p=0.016). The median survival time was 13.84 months (range=0.69-125.19 months) in malnourished patients (PA<5.0) compared to 51.16 months (range=7.02-116.79 months) in normally nourished head and neck cancer (HNC) patients (PA>5.0). Age adjusted body mass index had a similar impact on prognosis, but was not statistically significant (p=0.068) in the investigated study groups. CONCLUSION: BIA is able to document the impact of malnutrition on the survival of head and neck cancer patients.

Influence of amifostine on late radiation-toxicity in head and neck cancer--a follow-up study.

AIM: The late toxicities due to multimodal therapy of advanced head and neck cancers were analysed. The impact of cytoprotection with amifostine is the specific objective of this report. PATIENTS AND METHODS: A total of 851 patients (717 men, 134 women) with head and neck cancer were included in this prospective study. Of these patients, 519/851 had received amifostine before radio(chemo)therapy, while 332 control patients had not received any kind of cytoprotection before irradiation. Primary radiochemotherapy was performed in 282 patients and adjuvant radiation was administered in 569. The follow-up examination was carried out at our outpatient department 21.4 months (median, range 2.3 to 149 months) after the primary therapy. RESULTS: Late xerostomia was seen in 765/851 patients (89.9%). Altered taste was reported by 284/851 (33.5%). These symptoms were reduced significantly by amifostine. No influence was seen on interstitial lymph edema (48.4%), or stenosis of the cervical esophagus (20.4%). Secondary symptoms such as dysphagia (78.8%) also had a trend for reduction. CONCLUSION: The administration of amifostine offers an opportunity to reduce selected long-term toxicities for survivors of head and neck cancer.

Zinc concentrations in serum during head and neck cancer progression.

UNLABELLED: Reduced serum-zinc concentrations are well known as typical laboratory characteristics in advanced head and neck cancer. Our aim was to follow the development of this phenomenon during the disease. PATIENTS AND METHODS: A total of 21 patients were included in this pilot-study (1 female, 20 male). The median age was 64 years, range 43-80 years. The following tumour localizations were registered: 11 larynx, 4 oropharynx, 2 hypopharynx and 4 other. Serum zinc levels were registered at baseline and during the follow-up investigations using flame atomic absorption spectrometry. RESULTS: The median follow-up time was 17 months, range 6-43 months. During the follow-up, 9/21 patients died tumour-dependently, 2 patients were living with cancer, 8 patients showed NED, and a further 2 patients died of non-cancer related causes. The zinc concentration decreased from 0.76 mmol/l (0.48-1.07 mmol/l) to 0.55 mmol/l (0.32-1.01 mmol/l). Nine of 11 patients with cancer developed extremely low serum zinc concentration 4-6 weeks before dying. CONCLUSION: The serum zinc concentration may be a marker for definitive palliative situations in head and neck cancer patients.

Effect of Whole-abdominal Irradiation on Penetration Depth of Doxorubicin in Normal Tissue After Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in a Post-mortem Swine Model.

BACKGROUND: This study was performed to evaluate the impact of whole-abdominal irradiation on local penetration of doxorubicin into the peritoneum and the abdominal organs in a post-mortem swine model. MATERIALS AND METHODS: Doxorubicin was aerosolized into the abdominal cavity of swine at a pressure of 12 mmHg CO2 at room temperature (25°). One swine was subjected to pressurized intraperitoneal aerosol chemotherapy (PIPAC) using Micropump© without irradiation; the second one received 2 Gy and the third one 7 Gy whole-abdominal irradiation, 15 min prior to PIPAC application. Samples of the peritoneal surface were extracted at different positions from within the abdominal cavity. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. RESULTS: The depth of penetration of doxorubicin was found to be wide-ranging, between 17 µm on the surface of the stomach and 348 µm in the small intestine. The penetration depth into the small intestine was 348 µm, 312 µm and 265 µm for PIPAC alone, PIPAC with 2 Gy irradiation and PIPAC with 7 Gy irradiation, respectively (p<0.05). The penetration into the liver was 64 µm, 55 µm and 40 µm, respectively (p=0.05). CONCLUSION: Irradiation was not found to increase the depth of doxorubicin penetration into normal tissue in the post-mortem swine model. A reduction of doxorubicin penetration was observed after application of higher irradiation doses. Further studies are warranted to determine if irradiation can be used safely as chemopotentiating agent for patients with peritoneal metastases treated with PIPAC.

Sport in the Rehabilitation of Patients After Total Laryngectomy.

AIM: Laryngectomy due to cancer leads to decreased physical activity of patients. Rehabilitation programs focus on the improvement of voice and swallowing but the role of rehabilitation sports for such patients is unknown. PATIENTS AND METHODS: We interviewed all 38 patients (five women, 33 men; median age 56 years) of our patient's advocacy group. All had undergone laryngectomy because of cancer. We asked them to report their sporting activities and summarized their descriptions. RESULTS: Overall, 12 patients were members of our swimming group and had performed aqua gymnastics and swimming training in order to stabilize or improve the muscle structures of the neck and backbone. A further four patients only took part in swimming training. The training frequency was twice per month; when patients were introduced to the program, they increased this frequency to 4-5/month. Three patients started cycling with mountain bikes covering distances of between 30 and 50 km. A further two patients were able to follow our cycling program using e-bikes. Twenty patients reported walking weekly between 10 and 16 km. All patients summarized the positive impact of sports on their personal well-being. CONCLUSION: Swimming, aqua-fitness, cycling and (Nordic) walking are favourable sport disciplines for patients after laryngectomy for laryngeal cancer. Special training programs should be developed and included in rehabilitation procedures for patients after multimodal therapy of laryngeal cancer.

Irradiation Does Not Increase the Penetration Depth of Doxorubicin in Normal Tissue After Pressurized Intra-peritoneal Aerosol Chemotherapy (PIPAC) in an Ex Vivo Model.

AIM: To compare the impact of single fractional with bi-fractional irradiation on the depth of doxorubicin penetration into the normal tissue after pressurized intra-peritoneal aerosol chemotherapy (PIPAC) in our ex vivo model. MATERIALS AND METHODS: Fresh post mortem swine peritoneum was cut into 12 proportional sections. Two control samples were treated with PIPAC only (no irradiation), one sample on day 1, the other on day 2. Five samples were irradiated with 1, 2, 4, 7 or 14 Gy followed by PIPAC. Four samples were treated on day one with 0.5, 1, 2, 3.5 or 7 Gy and with the same radiation dose 24 h later followed by PIPAC. Doxorubicin was aerosolized in an ex vivo PIPAC model at 12 mmHg/36°C. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. RESULTS: Doxorubicin penetration (DP) after PIPAC for the control samples was 407 µm and 373 µm, respectively. DP for samples with single fraction irradiation was 396 µm after 1 Gy, 384 µm after 2 Gy, 327 µm after 4 Gy, 280 µm after 7 Gy and 243 µm after 14 Gy. DP for samples with 2 fractions of irradiation was 376 µm after 0.5+0.5 Gy, 363 µm after 1+1 Gy, 372 µm after 2+2 Gy, 341 µm after 3.5+3.5 and 301 µm after 7+7 Gy irradiation. Fractionating of the irradiation did not significantly change DP into normal tissue. CONCLUSION: Irradiation does not increase the penetration depth of doxorubicin into the normal tissue but might have a limiting impact on penetration and distribution of doxorubicin. Further studies are warranted to investigate the impact of addition of irradiation to PIPAC of tumor cells and to find out if irradiation can be used safely as chemopotenting agent for patients with peritoneal metastases treated with PIPAC.

Serum selenium in head and neck cancer patients--a new marker of tumor activity?

OBJECTIVE: The purpose of this work was to investigate the relationship between the tumor volume and the endogenous selenium levels in untreated head and neck cancer patients. MATERIALS AND METHODS: One hundred consecutive patients were included in this study. We measured the endogenous levels of selenium in the serum and the whole blood of all patients by atomic absorption spectrometry. Additionally, the activity of glutathione peroxidase and the concentration of malonedialdehyde were observed. The resectability of the tumor was used as an independent marker of the tumor volume. RESULTS: Thirty-one out of 100 patients had resectable tumors, while 69 patients were characterized as unresectable. The following median results were obtained (resectable versus unresectable): Serum Se 0.90 micromol/l versus 0.78 micromol/l (p=0.024); whole blood Se 1.00 micromol/l versus 0.93 micromol/l (p=0.139); glutathione peroxidase 145 U/l versus 148 U/l (p=0.93); and malonedialdehyde 2.21 mmol/l versus 2.6 mmol/l (p=0.84). CONCLUSION: The concentration of serum selenium shows a significant relationship with tumor resectability in patients with advanced head and neck cancer.

The prognostic value of irradiated lung volumes on the prediction of intra-/ post-operative mortality in patients after neoadjuvant radiochemotherapy for esophageal cancer. A retrospective multicenter study.

PURPOSE: To assess the association between dosimetric factors of the lung and incidence of intra- and postoperative mortality among esophageal cancer (EC) patients treated with neoadjuvant radiochemotherapy (N-RCT) followed by surgery (S). METHODS AND MATERIALS: Inclusion criteria were: age < 85 years, no distant metastases at the time of diagnosis, no induction chemotherapy, conformal radiotherapy, total dose ≤ 50.4 Gy, and available dose volume histogram (DVH) data. One-hundred thirty-five patients met our inclusion criteria. Median age was 62 years. N-RCT consisted of 36 - 50.4 Gy (median 45 Gy), 1.8 - 2 Gy per fraction. Concomitant chemotherapy consisted of 5-Fluoruracil (5-FU) and cisplatin in 113 patients and cisplatin and taxan-derivates in 15 patients. Seven patients received a single cytotoxic agent. In 130 patients an abdominothoracal and in 5 patients a transhiatal resection was performed. The following dosimetric parameters were generated from the total lung DVH: mean dose, V5, V10, V15, V20, V30, V40, V45 and V50. The primary endpoint was the rate of intra- and postoperative mortality (from the start of N-RCT to 60 days after surgical resection). RESULTS: A total of ten postoperative deaths (7%) were observed: 3 within 30 days (2%) and 7 between 30 and 60 days after surgical intervention (5%); no patient died during the operation. In the univariate analysis, weight loss (≥10% in 6 months prior to diagnosis, risk ratio: 1.60, 95%CI: 0.856-2.992, p=0.043), Eastern Cooperative Oncology Group-performance status (ECOG 2 vs. 1, risk ratio: 1.931, 95%CI: 0.898-4.150, p=0.018) and postoperative pulmonary plus non-pulmonary complications (risk ratio: 2.533, 95%CI: 0.978-6.563, p=0.004) were significantly associated with postoperative mortality. There was no significant association between postoperative mortality and irradiated lung volumes. Lung V45 was the only variable which was significantly associated with higher incidence of postoperative pulmonary plus non-pulmonary complications (Exp(B): 1.285, 95%CI 1.029-1.606, p=0.027), but not with the postoperative pulmonary complications (Exp(B): 1.249, 95%CI 0.999-1.561, p=0.051). CONCLUSIONS: Irradiated lung volumes did not show relevant associations with intra- and postoperative mortality of patients treated with moderate dose (36 - 50.4 Gy) conventionally fractionated conformal radiotherapy combined with widely used radiosensitizers. Postoperative mortality was significantly associated with greater weight loss, poor performance status and development of postoperative complications, but not with treatment-related factors. Limiting the volume of lung receiving higher radiation doses appears prudent because of the observed association with risk of postoperative complications.

Selenium in the treatment of radiation-associated secondary lymphedema.

PURPOSE: The aim of this explorative study was to evaluate the impact of selenium in the treatment of lymphedema after radiotherapy. MATERIALS AND METHODS: Between June 1996 and June 2001, 12 patients with edema of the arm and 36 patients with edema of the head-and-neck region were treated with selenium for therapy-related lymphedema. Of these 36 patients, 20 had interstitial endolaryngeal edema associated with stridor and dyspnea. All patients received sodium selenite over 4 to 6 weeks. RESULTS: Self-assessment using a visual analog scale (n = 48) showed a reduction of 4.3 points when comparing pre- and posttreatment values (p < 0.05). Of 20 patients with endolaryngeal edema, 13 underwent no tracheostomy, 5 underwent a temporary tracheostomy, and only 2 underwent a permanent tracheostomy. Ten of 12 patients with arm edema showed a circumference reduction of the edematous limb and improvement in the Skin-Fold Index by 23.3 points. An improvement of one stage or more was shown by the Földi or the Miller score (n = 28) in 22 (Földi score) and in 24 (Miller score) patients. CONCLUSIONS: Treatment with sodium selenite is well tolerated and easy to deliver. Additionally, our results suggest that sodium selenite has a positive effect on secondary-developing lymphedema caused by radiation therapy alone or by irradiation after surgery.

Combined radiotherapy and temozolomide in patients with recurrent high grade glioma.

AIMS AND BACKGROUND: There is only little preliminary information about combined-modality treatment with radiotherapy and temozolamide. The purpose of this analysis was to document the feasibility of such combined-modality treatment. METHODS: We treated 25 patients with recurrent high grade gliomas after standard therapy (surgery and radiation) with the following schedule: 400 mg temozolomide orally for five days repeated every 28 days, and radiotherapy at a dose of 20-30 Gy (2 x 1.2 Gy per day). Four of these patients underwent a second operation without complete tumor resection. RESULTS: After 125 courses of temozolomide, grade 1 (NCI-CTC) thrombocytopenia was found in four patients and grade 2 in two patients. Two patients developed grade 1 leukocytopenia and two others grade 2. CTC grade 1-2 nausea was observed in eight patients. For one patient we reduced the dose of temozolomide to 300 mg/day because of thrombocytopenia. One patient discontinued therapy after the first course because of leukocytopenia and nausea. CTC grade 3-4 side effects did not occur. Combined-modality treatment showed no more side effects than treatment with temozolomide alone. The median duration of response was seven months. CONCLUSION: The observed side effects were tolerable. Combined treatment with radiotherapy and temozolomide is feasible. Further investigation of this agent is necessary.