Evaluation of quality of life in lung cancer patients receiving radiation and Viscum album L.: a real-world data study.

BACKGROUND: Lung cancer (LC) is associated with high mortality and poor quality of life (QoL). The disease as well as oncological treatments such as radiation and chemotherapy with adverse effects can impair the QoL of patients. Add-on treatment with extracts of Viscum album L. (white-berry European mistletoe, VA) has been shown to be feasible and safe and to improve the QoL of cancer patients. The aim of this study was to analyze the changes in QoL of LC patients being treated with radiation according to oncological guidelines and add-on VA treatment in a real-world setting. METHODS: A real-world data study was conducted using registry data. Self-reported QoL was assessed by the evaluation of the European Organization of Research and Treatment Health-Related Quality of Life Core Questionnaire scale (EORTC QLQ-C30). Adjusted multivariate linear regression analyses were performed to analyze factors associated with changes in QoL at 12 months. RESULTS: A total of 112 primary LC patients (all stages, 92% non-small-cell lung cancer, median age 70 (ICR: 63-75)), answered the questionnaires at first diagnosis and 12 months later. Assessment of 12 months changes in QoL revealed significant improvement of 27 points for pain (p = 0.006) and 17 points for nausea/vomiting (p = 0.005) in patients who received combined radiation and VA. In addition, significant improvements of 15 to 21 points for role (p = 0.03), physical (p = 0.02), cognitive (p = 0.04), and social functioning (p = 0.04) were observed in guideline treated patients receiving no radiation but add-on VA. CONCLUSIONS: Add-on VA therapy reveals supportive effects for the QoL of LC patients. Particularly in combination with radiation a significant reduction in pain and nausea/ vomiting has been observed. Trial registration The study received ethics approval and was retrospectively registered (DRKS00013335 on 27/11/2017).

Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy (CIPN) with Non-Pharmacological Interventions: Clinical Recommendations from a Systematic Scoping Review and an Expert Consensus Process.

Background: Most individuals affected by cancer who are treated with certain chemotherapies suffer of CIPN. Therefore, there is a high patient and provider interest in complementary non-pharmacological therapies, but its evidence base has not yet been clearly pointed out in the context of CIPN. Methods: The results of a scoping review overviewing the published clinical evidence on the application of complementary therapies for improving the complex CIPN symptomatology are synthesized with the recommendations of an expert consensus process aiming to draw attention to supportive strategies for CIPN. The scoping review, registered at PROSPERO 2020 (CRD 42020165851), followed the PRISMA-ScR and JBI guidelines. Relevant studies published in Pubmed/MEDLINE, PsycINFO, PEDro, Cochrane CENTRAL, and CINAHL between 2000 and 2021 were included. CASP was used to evaluate the methodologic quality of the studies. Results: Seventy-five studies with mixed study quality met the inclusion criteria. Manipulative therapies (including massage, reflexology, therapeutic touch), rhythmical embrocations, movement and mind-body therapies, acupuncture/acupressure, and TENS/Scrambler therapy were the most frequently analyzed in research and may be effective treatment options for CIPN. The expert panel approved 17 supportive interventions, most of them were phytotherapeutic interventions including external applications and cryotherapy, hydrotherapy, and tactile stimulation. More than two-thirds of the consented interventions were rated with moderate to high perceived clinical effectiveness in therapeutic use. Conclusions: The evidence of both the review and the expert panel supports a variety of complementary procedures regarding the supportive treatment of CIPN; however, the application on patients should be individually weighed in each case. Based on this meta-synthesis, interprofessional healthcare teams may open up a dialogue with patients interested in non-pharmacological treatment options to tailor complementary counselling and treatments to their needs.

Cisplatin Versus Carboplatin and Paclitaxel in Radiochemotherapy for Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: The implementation of a platinum-containing regimen is recommended for definitive and adjuvant therapy of patients with locally advanced head and neck tumour. We compared the conditions for the use of cisplatin or carboplatin/paclitaxel or for changing between these two regimens on a clinic-specific basis. PATIENTS AND METHODS: We evaluated 150 patients with advanced head and neck squamous cell carcinoma who received simultaneous radiochemotherapy at our institution between 2012 and 2017. Chemotherapy with weekly doses of cisplatin (40 mg/m2, group 1) or, in cases of impaired renal and/or cardiac function, with weekly doses of carboplatin AUC2 and paclitaxel (45 mg/m2, group 2), was performed as a first-choice therapy. If toxicities occurred in group 1, treatment was switched to the carboplatin/paclitaxel regimen (group 3). Patient- and therapy-related parameters, toxicity and survival data were compared across groups. RESULTS: We examined 99, 30, and 21 patients in each group who received at least 1 course of chemotherapy. Group 3 patients switched from cisplatin to carboplatin/paclitaxel after a median of 3 courses due to nephrotoxicity (95.2%). The target of at least 5 chemotherapy courses was most frequently achieved by patients in group 1 (69.7%), followed by group 3 (61.9%) and then group 2 (40.0%). Multivariate analysis revealed that patients who switched groups were more likely to be over 60 years old (p=0.021), undergo definitive radiochemotherapy (p=0.049) and develop higher nephrotoxicity (p=0.036) than group 1 patients. Outcomes did not differ between groups. CONCLUSION: When cisplatin application is contraindicated due to renal- or cardiotoxicity, carboplatin/paclitaxel is an appropriate option.

Effects of an Interdisciplinary Integrative Oncology Group-Based Program to Strengthen Resilience and Improve Quality of Life in Cancer Patients: Results of a Prospective Longitudinal Single-Center Study.

BACKGROUND: Patients with cancer receiving oncological treatment often suffer from a reduced quality of life (QoL) and resilience. OBJECTIVES: The aim of this study was to evaluate the effect of an interdisciplinary integrative oncology group-based program on resilience and quality of life in patients with cancer during or after conventional oncological therapy. METHODS: This prospective longitudinal single-center study evaluated the resilience (Resilience Scale), quality of life (EORTC-QLQ C30), anxiety, depression (Hospital Anxiety and Depression Scale), and distress levels (Distress Thermometer) of 60 patients with cancer who participated in a 10-week interdisciplinary integrative oncology group-based program during or after cancer treatment in outpatient clinics. An average of 12 (range 11-13) patients participated in each 10-week group. The program included recommendations for diet, stress management, relaxation, and exercise, as well as naturopathic self-help strategies and psychosocial support. RESULTS: There were slight increases in global quality of life scores (week 0: 58.05 ± 20.05 vs week 10: 63.13 ± 18.51, n = 59, P = .063, d = -.25) and resilience scores (week 0: 63.50 ± 13.14 vs week 10: 66.15 ± 10.17, n = 52, P = .222, d = -.17) after the group program compared to before; however, these changes were not statistically significant and had small effect sizes. Patients with at least moderate anxiety symptoms (P = .022, d = .42) and low resilience (P = .006, d = -.54) benefited most from the program. The patients reported no relevant side effects or adverse events from the program. CONCLUSIONS: No significant effects on global quality of life or resilience were found in the general sample; notably, patients with anxiety and low initial resilience benefited the most from the program.

Evaluation of treatment-associated eye toxicity after irradiation in childhood and adolescence-results from the Registry of the Evaluation of Side Effects after Radiotherapy in Childhood and Adolescence (RiSK).

PURPOSE: The aim of the study is to evaluate treatment-related acute and late eye toxicity associated with radiation therapy in childhood and adolescence as correlated with RT (radiotherapy) doses. METHODS: From 2001 to 2016, a total of 1725 children and adolescents undergoing radiation therapy were prospectively documented in the Registry of the Evaluation of Side Effects after Radiotherapy in Childhood and Adolescence (RiSK). The RTOG/EORTC criteria were used to classify ocular acute and late effects. Uni- and multivariate analyses were carried out to evaluate the impact of patient age, pre-existing impairments, and radiation dose on ocular toxicity. RESULTS: Of all documented patients, 593 received dose to the eye and formed the basis of this analysis. In 435 patients, information on acute reaction was available and graded 1, 2, 3, and 4 in 49, 17, 0, and 2 patients, respectively. Information on late toxicity was available in 268 patients and graded 1, 2, 3, and 4 in 15, 11, 11, and 5 patients, respectively. The acute toxicity rate was significantly higher in children who received a maximum dose > 50 Gy to the eye (p < 0.001) and who had a pre-existing eye impairment (p < 0.001 in multivariate analysis). The development of late toxicity was significantly higher for patients experiencing acute toxicity and having received a radiation dose > 50 Gy. CONCLUSION: Acute and late toxicity both correlate with high radiation dose to the eye (> 50 Gy) and acute toxicity additionally with pre-existing eye impairments.

Nursing Procedures for the Prevention and Treatment of Mucositis Induced by Cancer Therapies: Clinical Practice Guideline Based on an Interdisciplinary Consensus Process and a Systematic Literature Search.

BACKGROUND: Patients with cancer receiving tumor therapy often suffer from oral mucositis. OBJECTIVES: The aim of this project was to summarize experiences with nursing procedures by experts in integrative oncology and to establish recommendations for nursing interventions that can prevent or cure mucositis. METHODS: The study design was an interdisciplinary consensus process based on a systematic literature search. RESULTS: The panel discussed and agreed on 19 nursing procedures, which included mouthwashes, such as teas, supplements, oil applications, and different kinds of ice cubes to suck, as well as flaxseed solution, propolis, and mare milk. Twelve interventions were classified as effective, with effectiveness for OraLife, propolis, sea buckthorn pulp oil, marshmallow root tea also for xerostomia, Helago chamomile oil, mare milk, and Saliva Natura rated as highly effective in clinical experience. In the systematic literature search, a total of 12 out of 329 randomized controlled trials and meta-analyses on chamomile (n = 3), Calendula (n = 1) and sage (n = 1), propolis (n = 2), and sucking ice cubes (cryotherapy; n = 5) met all inclusion criteria. Trial evidence for effectiveness in oral mucositis was revealed for propolis and cryotherapy. CONCLUSIONS: The current evidence supports the use of some nursing procedures (f.e. propolis for 2 and 3 grade mucositis) for improving oral mucositis during cancer therapies. There is still a need to define general clinical practice guidelines for the supportive treatment of mucositis, as well as for more interdisciplinary research in this area.

Are women more afraid than men? Fear of recurrence in couples with cancer - predictors and sex-role-specific differences.

PURPOSE: Although fear of cancer recurrence (FoR) is one of the major concerns in cancer patients and their partners with approximately 49% reporting moderate to high FoR, few studies investigated predictors and sex-role-specific differences. The aim of the current study was to investigate FoR in couples with different types of cancer and to gain a deeper understanding of sex and role-specific differences and predictors of FoR in patients and partners. DESIGN: Cross-sectional study in Germany. Sample: N = 188 couples with prostate (PC; n=52), laryngeal (LC; n=21) or breast cancer (BC; n=115) participated. All PC and LC patients were males, all BC patients were females. METHODS: Fear of recurrence, depression, and relationship satisfaction were measured with validated questionnaires (Fear of Progression Questionnaire, Patient Health Questionnaire, Hospital Anxiety and Depression Scale, Quality of Marriage Index) in couples with PC, LC, or BC. FINDINGS: Results indicated sex-role-specific differences. For women, FoR was higher for patients (M = 35.76) than for caregivers (M = 27.11). For males, spouses of women with BC (M = 30.1) showed higher FoR than male PC or LC patients (M = 24.9). Moreover, in couples there was a correlation between the FoR of one and the other (PC: r = .51, BC: r = .31, LC: r = .41). Depression was as a significant predictor, with a positive relationship to FoR. Moreover, in men with PC and LC besides depression, age emerged as significant predictor with a negative relationship to FoR. The Actor-Partner-Interdependence-Model showed for couples with PC or LC significant actor effects, both for patients and partners. Moreover, a significant partner effect emerged for patients' depression on partners' FoR. For couples with BC only significant actor effects occurred. CONCLUSIONS: FoR remains a major concern for both cancer patients and their partners. Implications for Psychosocial Providers or Policy: FoR should be considered both in cancer patients and their spouses. In addition, sex and role effects should be taken into account in treatment of FoR.

Body image in men with prostate or laryngeal cancer and their female partners.

Objectives: The study examines body image of male cancer patients and their female partners as well as factors influencing body image. Methods: N = 73 heterosexual couples in which the male partner was diagnosed with prostate (PC; n = 52) or laryngeal cancer (LC; n = 21) completed questionnaires on body image acceptance (Self Image Scale), relationship satisfaction (Quality of Marriage Questionnaire), and cancer-related distress (Questionnaire on Stress in Cancer Patients). The body image was assessed from two perspectives: self-acceptance (which measures a person's satisfaction or acceptance of the body) and partner-acceptance (which assesses a person's perception of the partners' appraisals of the body). Results: No differences occurred in body image acceptance between men with PC or LC. Patients with PC rated the perceived partner-acceptance lower than did their female partners. In couples with LC, women rated the self-acceptance of their partners higher than did the patients themselves. Multiple regression analysis revealed that for survivors of PC, cancer-related distress, relationship satisfaction and partner-acceptance emerged as significant predictors of self-acceptance. The only significant predictor of partner-acceptance was men's self-acceptance. Conclusions: The dissatisfaction with physical appearance is found in PK and LK patients and seems to persist for a long time. Impairment of patients' body image should be identified and addressed to prevent the negative effects on psychosocial stress for patients and relationship satisfaction.

Quality of life in patients with limited (1-3) brain metastases undergoing stereotactic or whole brain radiotherapy : A prospective study of the DEGRO QoL working group.

PURPOSE: Published results of quality of life (QoL) studies mostly concern whole brain radiotherapy for limited or multiple brain metastases. This prospective multicentre study was designed to compare the QoL of patients with limited (1-3) brain metastases treated with either whole brain (WBRT) or stereotactic radiotherapy (SRT). METHODS: From 01/2007-03/2011, 90 limited brain metastases patients who were previously untreated (n = 77) or had undergone primary surgery (n = 13) were recruited at 14 centres in Germany and Austria. QoL was measured with the EORTC-QLQ-C15-PAL and BN20 brain modules before the start of radiotherapy and after 3 months. RESULTS: Fifty-two patients (58%) received WBRT and 38 (42%) received SRT. At 3 months, 67 patients (74%) were still living, and 92.6% of the 3­month survivors completed the second set of questionnaires. Analysis of the QLQ-C15-PAL and BN20 scales revealed significant deterioration in patients treated with WBRT and SRT in physical function (p < 0.001 and p = 0.007), fatigue (p < 0.001 and p = 0.036), nausea (p = 0.003 and p = 0.002), appetite loss (p < 0.001 and p = 0.025), drowsiness (p < 0.001 and p = 0.011), hair loss (p = 0.019 and p = 0.023) and itchy skin (p = 0.030 and p = 0.018). Motor dysfunction (p < 0.001), communication deficits (p = 0.002) and leg weakness (p < 0.001) declined significantly only in patients treated with WBRT. Comparing the two radiotherapy techniques over time, the results showed significant differences in symptom scores for future uncertainty, fatigue and appetite loss. CONCLUSIONS: QoL data as an outcome of the paper should be considered in decision making on the irradiation technique in patients with small number of brain metastases. Larger studies are required to verify the results according to subgroups.

Frequency and risk factors for arm lymphedema after multimodal breast-conserving treatment of nodal positive breast Cancer - a long-term observation.

BACKGROUND: Arm-lymphedema is a major complication after breast cancer. Recent studies demonstrate the validity of predicting Breast Cancer Related Lymphedema (BCRL) by self-reports. We aimed to investigate the rate of BCRL and its risk factors in the long-term using self-reported symptoms. METHODS: Data was collected from 385 patients who underwent multimodal therapy for nodal positive breast cancer, including breast conserving surgery, axillary dissection, and local or locoregional radiotherapy. Two validated questionnaires were used for the survey of BCRL (i.e. LBCQ-D and SDBC-D). These were analysed collectively with retrospective data of our medical records. RESULTS: 23.5% (n = 43) suffered a permanent BCRL (stage II-III) after a median follow-up time of 10.1 years (4.9-15.9 years); further 11.5% (n = 23) reported at least one episode of reversible BCRL (Stage 0-I) during the follow-up time. 87.1% of the patients with lymphedema developed this condition in the first two years. Adjuvant chemotherapy was a significant risk factor for the appearance of BCRL (p = 0.001; 95%-CI 7.7-10.2). CONCLUSIONS: Breast cancer survivors face a high risk of BCRL, particularly if axillary dissection was carried out. Almost 90% of BCRL occurred during the first two years after radiotherapy. Self-report of symptoms seems to be a suitable instrument of early detection of BCRL.

Late Effects and Long-Term Follow-Up after Cancer in Childhood.

Today, 80% of children and adolescents with cancer survive their disease. From the results of aftercare research arises the question: Are the survivors also healthy? Many late effects depend on the type of cancer and its treatment. Patients with brain tumors and with malignant sarcomas are very often affected by secondary diseases. Data from the USA report that around 2/3 of all patients still living 30 years after their cancer treatment in childhood suffer from late complications. Equivalent figures for Germany were previously unavailable. In accordance with the guidelines, regular follow-ups to diagnose a relapse or possible late effects have mostly been carried out in the primary children's hospitals. In adolescence and in young adulthood, this regimen does no longer serve the patients' mental and physical needs. To ensure appropriate care for this maturing patient group, interdisciplinary approaches (e.g., aftercare consultations) are required in which pediatric oncologists collaborate with colleagues from the field of internal medicine and other disciplines. Individual, risk-adapted (depending on the cancer treatment) aftercare plans based on pre-existing aftercare recommendations must be drawn up for every patient and to secure the early diagnosis of possible late effects. The conservation of health and quality of life after cancer treatment (in all age groups) will in the future not only represent a social but also an economic consideration.

Lung toxicity after radiation in childhood: Results of the International Project on Prospective Analysis of Radiotoxicity in Childhood and Adolescence.

BACKGROUND AND PURPOSE: This study presents the evaluation of acute and late toxicities of the lung in children and adolescents after irradiation in terms of dose-volume effects. MATERIALS AND METHODS: Irradiated children and adolescents in Germany have prospectively been documented since 2001 in the "Registry for the Evaluation of Side-Effects after Radiotherapy in Childhood and Adolescence (RiSK)"; in Sweden since 2008 in the RADTOX registry. RESULTS: Up to April 2012, 1,392 children were recruited from RiSK, and up to June 2013, 485 from the RADTOX-registry. Of these patients, 295 were irradiated to the lung. Information about acute toxicity was available for 228 patients. 179 patients have been documented concerning late toxicity (≥grade 1: n = 28). The acute toxicity rate was noticeably higher in children irradiated with 5-20Gy (p < 0.05). In the univariate analysis, a shorter time until late toxicity was noticeably associated with irradiation with 5-15Gy (p < 0.05). CONCLUSION: Acute and late toxicities appear to be correlated with higher irradiation volumes and low doses. Our data indicate that similar to the situation in adult patients, V5, V10, V15 and V20 should be kept as low as possible (e.g., at least V5 < 50%, V10 and V15 < 35% and V20 < 30%) in children and adolescents to lower the risk of toxicity.

Impact of Time Factors on Outcome in Patients with Head and Neck Cancer Treated with Definitive Radio(Chemo)Therapy.

AIM: To evaluate treatment-related factors such as overall treatment time (OTT) and radiation treatment time (RTT) in head-and-neck cancer. PATIENTS AND METHODS: A total of 216 patients with locoregionally advanced inoperable head and neck cancer were treated with definitive radio(chemo)therapy. Mean follow-up was 37 months. RESULTS: Median time from diagnosis to start of radiotherapy (total waiting time) was 34 days, and comprised of referral waiting time and time for preparatory work. Median RTT was 40 days, and median OTT was 91 days. At 6, 12 and 24 months local recurrence-free survival (LRFS) was 75%, 65% and 60%; metastasis-free survival (MFS) was 84%, 77% and 70%; overall survival (OS) was 72%, 58% and 40%. Tumor stage, boost and chemotherapy were significant for OS, waiting time for preparatory work and RTT were significant for MFS, and referral waiting time and total radiotherapy dose for LRFS. CONCLUSION: RTT ≤40 days was a prognostic factor for better MFS. Prolonged waiting time had a converse effect for radiotherapy with better outcome on MFS and LRFS.

New concepts of personalized therapy in salivary gland carcinomas.

Salivary gland carcinomas are rare tumours and therapy strategies are less standardized than in lung, gastric or breast cancer. Therapy is based on surgery, but not all carcinomas are completely resectable, e.g. because carcinomas often show infiltration of nerves. For further therapy decision pathology is recommended, but evaluation of potential targets for personalized therapy is not part of the routine panel. Many salivary gland carcinomas can be resistant to radio- and/or chemotherapy, which limits therapeutic options. This review summarizes new concepts for personalized therapy in salivary gland carcinoma patients. Targeting growth receptors HER2, EGFR, AR and ER is possible but, in some studies, potential target molecules were not adequately tested before therapy. In addition, approximately 20-25% of carcinomas have RAS mutation (mainly H-RAS), which could explain resistance to therapy. Possible therapy options in the future could be immunomodulation (inhibition of PDL1/PD1 signalling), nanoparticles (gold nanoparticles conjugated to cetuximab can increase radiosensitivity) and drug delivery systems (trastuzumab emtansine/T-DM1).

A novel germline POLE mutation causes an early onset cancer prone syndrome mimicking constitutional mismatch repair deficiency.

In a 14-year-old boy with polyposis and rectosigmoid carcinoma, we identified a novel POLE germline mutation, p.(Val411Leu), previously found as recurrent somatic mutation in 'ultramutated' sporadic cancers. This is the youngest reported cancer patient with polymerase proofreading-associated polyposis indicating that POLE mutation p.(Val411Leu) may confer a more severe phenotype than previously reported POLE and POLD1 germline mutations. The patient had multiple café-au-lait macules and a pilomatricoma mimicking the clinical phenotype of constitutional mismatch repair deficiency. We hypothesize that these skin features may be common to different types of constitutional DNA repair defects associated with polyposis and early-onset cancer.

Acute Toxicity Grade 3 and 4 After Irradiation in Children and Adolescents: Results From the IPPARCA Collaboration.

PURPOSE: In the context of oncologic therapy for children, radiation therapy is frequently indicated. This study identified the frequency of and reasons for the development of high-grade acute toxicity and possible sequelae. MATERIALS AND METHODS: Irradiated children have been prospectively documented since 2001 in the Registry for the Evaluation of Side Effects After Radiation in Childhood and Adolescence (RiSK) database in Germany and since 2008 in the registry for radiation therapy toxicity (RADTOX) in Sweden. Data were collected using standardized, published forms. Toxicity classification was based on Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. RESULTS: As of June 2013, 1500 children have been recruited into the RiSK database and 485 into the RADTOX registry leading to an analysis population of 1359 patients (age range 0-18). A total of 18.9% (n=257) of all investigated patients developed high-grade acute toxicity (grades 3/4). High-grade toxicity of the bone marrow was documented for 63.8% (n=201) of those patients, oral mucositis for 7.6% (n=24), and dermatitis for 7.6% (n=24). Patients with high-grade acute toxicity received concomitant chemotherapy more frequently (56%) than patients with no or lower acute toxicity (31.5%). In multivariate analyses, concomitant chemotherapy, diagnosis of Ewing sarcoma, and total radiation dose showed a statistically noticeable effect (P≤.05) on acute toxicity, whereas age, concomitant chemotherapy, Hodgkin lymphoma, Ewing sarcoma, total radiation dose, and acute toxicity influenced the time until maximal late toxicity. CONCLUSIONS: Generally, high-grade acute toxicity after irradiation in children and adolescence occurs in a moderate proportion of patients (18.9%). As anticipated, the probability of acute toxicity appeared to depend on the prescribed dose as well as concomitant chemotherapy. The occurrence of chronic toxicity correlates with the prior acute toxicity grade. Age seems to influence the time until maximal late toxicity but not the development of acute toxicity.

Hepatotoxicity after liver irradiation in children and adolescents : results from the RiSK.

AIM: The aim of this study was to evaluate acute and late radiotherapy-associated hepatotoxicity in consideration of dose-volume effects and liver function in childhood and adolescence. PATIENTS AND METHODS: Since 2001, irradiated children and adolescents in Germany have been prospectively documented in the "Register of Treatment-Associated Late Effects After Radiotherapy of Malignant Diseases in Childhood and Adolescence (RiSK)" using standardized forms. Toxicity was graded according to the Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: Until April 2012, 1,392 children and adolescents from 62 radiotherapy centers were recruited. In all, 216 patients underwent irradiation of the liver (median age 9 years, range 1-18 years, 70 patients with total-body irradiation, TBI). For 75 % of patients without TBI, information on acute toxicity of the liver was available: 24 patients had acute toxicity of grade 1-4 (grade 1, 2, and 4, in 20, 3, and 1 patient, respectively), including five patients receiving simultaneous hepatotoxic chemotherapy. Information on late toxicity was documented in 465 forms from 216 patients, with a median follow-up of 2 years. A maximum grade of toxicity of ≥ 0 occurred in 18 patients over time (with grade 1, 2, and 3 toxicity occurring in 15, 2, and 1 patient, respectively), including three patients (17 %) with TBI. One of them received simultaneous hepatotoxic chemotherapy. In multivariable analysis, volume-dose correlations showed no statistically noticeable effect on acute or chronic toxicity. CONCLUSION: Only low hepatotoxicity developed in children after irradiation of various abdominal and thoracic tumors. Due to the low radiation doses to the liver (median liver dose = 5 Gy) and the low toxicities that were consecutively observed, dose-volume curves for liver toxicity could not be established. These findings reflect the cautious attitude of radiation oncologists in terms of attributable liver doses in the treatment of the investigated tumor entities. It offers the option of increasing these conservative doses if tumor control is necessary.

High frequency of lobular breast cancer in distant metastases to the orbit.

Metastasis to the periocular soft tissue of the orbit is a rare manifestation of metastatic cancer. Infiltrating lobular breast cancer (ILBC) is a special breast cancer subtype, which accounts for 10-15% of all mammary carcinomas and for ~1% of all malignancies. Here, we report on a high frequency of lobular breast cancer in patients with orbital metastases identified in an original series of metastatic tumor specimens and by a systematic literature review. A series of 14 orbital metastases was compiled from formalin-fixed paraffin-embedded archival tissues. All cases were subjected to histological re-review and detailed immunophenotypical characterization. In addition, we performed a meta-analysis of 68 previously published case reports describing orbital metastases, with special reference to breast cancer subtypes. Based on clinical history, histomorphology, immunophenotype, and/or comparison with matched primary tumors, orbital metastases were derived from breast cancer in 8/14 cases, seven of which were classified as metastatic lobular breast cancer. Other entities included non-small cell lung cancer (4/14), infiltrating ductal breast cancer (1/14), prostate cancer (1/14) and adenocarcinoma of the esophagus (1/14). In line with this original series of orbital metastases, lobular breast cancer was the most common malignancy in 72 patients with orbital metastases described in 68 independent case reports. In conclusion, lobular breast cancer represents the cancer subtype with the highest prevalence among orbital metastases. The high frequency of ILBC in orbital metastases illustrates the special metastatic behavior of this tumor entity and may have implications for the understanding of the organotropism of metastatic lobular breast cancer.