Volumetric modulated arc therapy versus intensity-modulated proton therapy in the irradiation of infra diaphragmatic Hodgkin Lymphoma in female patients

Purpose To investigate the role of infra diaphragmatic intensity-modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT) for female Hodgkin Lymphoma (HL) patients and to estimate the risk of secondary cancer and ovarian failure. Methods A comparative treatment planning study was performed on 14 patients, and the results were compared according to conventional dose-volume metrics. In addition, estimates of the excess absolute risk (EAR) of secondary cancer induction were determined for the bowel, the bladder and the rectum. For the ovaries, the risk of ovarian failure was estimated. Results The dosimetric findings demonstrate the equivalence between VMAT and IMPT in terms of target coverage. A statistically significant reduction of the mean and near-to-maximum doses was proven for the organs at risk. The EAR ratio estimated for IMPT to VMAT was 0.51 +/- 0.32, 0.32 +/- 0.35 and 0.05 +/- 0.11 for the bowel, bladder and rectum, respectively. Concerning the risk of ovarian failure for the chronologic age ranging from 18 to 46 years, the expected net loss in fertility years ranged from 4.8 to 3.0 years for protons and 12.0 to 5.7 years for photons. Conclusion This in-silico study confirmed the beneficial role of IMPT from a dosimetric point of view. Mathematical models suggested that the use of protons might be further advantageous due to the expected reduction of the risk of secondary cancer induction and its milder impact on the reduction of fertility

Modern radiotherapy in Hodgkin's lymphoma

The treatment of mostly young patients with Hodgkin lymphoma (HL) in most cases leads to a permanent cure. Unlike no other disease, the continuous treatment of patients in clinical trials led to an ongoing optimization of therapy. The initial large field radiotherapy was reduced as well as the irradiation dosage and by the addition of chemotherapy the combined modality was established. A selective review of the available data on HL and radiotherapy was carried out based on the PubMed database. Current technical innovations and new target volume definitions strongly influence radiotherapy planning and execution more than ever. Due to the excellent prognosis of HL patients, long-term toxicity plays a pivotal role. Lung fibroses, cardiac infarction and secondary malignancies are possible side effects. Their risk can be influenced by a thorough radiotherapy planning and execution. Thus, techniques, such as deep inspiration breath hold (DIBH) and modern radiotherapy techniques, such as intensity modulated radiotherapy (IMRT) and image guided radiotherapy (IGRT) have a strong impact, very similar to the new target volume definitions of the International Lymphoma Radiation Oncology Group (ILROG). The use of improved techniques in radiotherapy planning and performance has made high precision radiotherapy feasible. Furthermore, current data suggest a positive influence on acute and long-term side effects

Chemoradiation for elderly patients (>= 65 years) with esophageal cancer: a retrospective single-center analysis

Background Present studies on the efficacy and safety of curative chemoradiation therapy (CRT) with esophageal cancer reflect heterogenous results especially in elderly patients. The aim of this study was to evaluate the toxicity and efficacy of CRT in patients >= 65 years. In a cohort, the focus centered around treatment-related toxicity (CTCAE Grade > 3), overall survival as well as progression free survival, comparing these rates in-between patients older than 70 years to those younger than 70 years. Methods A total of 67 patients older than 65 years (34 (50.7%) were older than 70 years) met the inclusion criteria for retrospective analysis (period from January 2013 to October 2017). Treatment consisted of radiotherapy and chemotherapy with carboplatin/paclitaxel or fluorouracil (5-FU)/cisplatin with the intention of neoadjuvant or definite chemoradiation. A sum of 67 patients received CRT (44 (65.6%) patients in neoadjuvant, 23 (34.4%) in definite intent). Of these, 22 and 12 patients were older than 70 years (50% and 52.2% in both treatment groups, respectively). Median age was 71 years and patients had a good physical performance status (ECOG 0: 57.6%, ECOG 1: 27.3%). Median follow-up was 24 months. Most patients had advanced tumour stages (T3 stage: n = 51, 79.7%) and nodal metastasis (N1 stage: n = 54, 88.5%). A subgroup comparison was conducted between patients aged 70 years. Results In severe (CTCAE Grade 3-5) toxicities (acute and late), no significant differences were observed between both patient groups ( 70 years). 21% had acute grade 3 events, 4 patients (4%) had grade 4 events, and two patients (3%) had one grade 5 event. Late toxicity after CRT was grade 1 in 13 patients (22%), grade 2 in two (3%), grade 3 in two (3%), grade 4 in four (7%), and grade 5 in one (2%). Median overall survival (OS) of all patients was 30 months and median progression-free survival (PFS) was 16 months. No significant differences were seen for OS (32 months vs. 25 months; p = 0.632) and PFS (16 months vs. 12 months; p = 0.696) between older patients treated with curative intent and younger ones. Trimodal therapy significantly prolonged both OS and PFS (p = 0.005; p = 0.018), regardless of age. Conclusion CRT in elderly patients (>= 65 years) with esophageal cancer is feasible and effective. Numbers for acute and late toxicities can be compared to cohorts of younger patients (< 65 years) with EC who received the same therapies. Age at treatment initiation alone should not be the determining factor. Instead, functional status, risk of treatment-related morbidities, life expectancy and patient ' s preferences should factor into the choice of therapy

The Role of Age and Comorbidities in Esophagogastric Cancer Chemoradiation of the Frail Elderly (>70 Years): An Analysis from a Tertiary High Volume-Center

Elderly patients > 70 years of age with esophageal cancer (EC) represent a challenging group as frailty and comorbidities need to be considered. The aim of this retrospective study was to evaluate the efficacy and side effects of curative chemoradiation therapy (CRT) with regard to basic geriatric screening in elderly patients in order to elucidate prognostic factors. Thirty-four elderly patients > 70 years with EC treated at our cancer center between May 2014 and October 2018 fulfilled the selection criteria for this retrospective analysis. Treatment consisted of intravenous infusion of carboplatin/paclitaxel or fluorouracil (5-FU)/cisplatin with the intention of neoadjuvant or definite chemoradiation. Clinicopathological data including performance status (ECOG), (age-adjusted) Charlson comorbidity index (CCI), Frailty-scale by Fried, Mini Nutritional Assessment Short Form, body mass index, C-reactive protein to albumin ratio, and treatment-related toxicity (CTCAE) were assessed. Data were analyzed as predictors of overall survival (OS) and progression-free survival (PFS). All patients (ten female, 24 male) received combined CRT (22 patients in neoadjuvant, 12 patients in definite intent). Median age was 75 years and the ECOG index between 0 and 1 (52.9% vs. 35.3%); four patients were rated as ECOG 3 (11.8%). Median follow-up was 24 months. Tumors were mainly located in the lower esophagus or esophagogastric-junction with an T3 stage (n = 25; 75.8%) and N1 stage (n = 28; 90.3%). 15 patients (44.1%) had SCC, 19 patients (55.9%) AC. 26 of the patients (76.5%) were scored as prefrail and 50% were in risk for malnutrition (n = 17). In relation to the BMI, ten patients (29.4%) were ranked as overweight, and 15 patients were presented in a healthy state of weight (44.1%). Grade 3 acute toxicity (or higher) occured in nine cases (26.5%). Most of the patients did not show any late toxicities (66.7%). Trimodal therapy provides a significant prolonged OS (p = 0.049) regardless of age, but without impact on PFS. Our analysis suggests that chemoradiation therapy is feasible for elderly patients (>70 years) with tolerable toxicity. Trimodal therapy of EC shows a positive effect on OS and PFS. Further studies are needed to elucidate benefitting subgroups within the elderly. In addition to age, treatment decisions should be based on performance status, nutritional condition and multidisciplinary validated geriatric screening tools

Involved-Field Radiation Therapy Prevents Recurrences in the Early Stages of Hodgkin Lymphoma in PET-Negative Patients After ABVD Chemotherapy: Relapse Analysis of GHSG Phase 3 HD16 Trial

Purpose: The HD16 trial of the German Hodgkin Study Group (NCT00736320) demonstrated that radiation therapy in early stage Hodgkin lymphoma without risk factors cannot be safely omitted, and therefore combined modality therapy (CMT) remains the standard treatment. To demonstrate the local effect of consolidating involved-field radiation therapy (IF-RT), we performed an analysis of the recurrence pattern of positron emission tomography (PET)-negative HD16 patients. Methods and Materials: Between 2009 and 2015, 1150 patients with early-stage Hodgkin lymphoma without risk factors were randomly assigned to PET guided to 20 Gy IF-RT after 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy in the HD16 study of the German Hodgkin Study Group. The study was designed as a prospective randomized controlled trial. We correlated the localization of recurrence with the panel-based IF-RT plan, which was drawn up for all patients prospectively, blinded to treatment allocation. Accordingly, we were able to identify recurrences that occurred at least in part inside or outside of the (potential) radiation field (in-field and out-field, respectively). Results: There were 328 and 300 PET-negative patients assigned to CMT and PET-guided treatment (ie, chemotherapy alone), respectively. Within a median 47-month follow-up, disease progression or recurrence was documented for 15 and 29 patients treated with and without IF-RT, respectively. Relapse localization was unknown in 1 CMT patient. Without IF-RT, 5-year inci-dence of in-field relapses was 10.5% (95% confidence interval, 6.5-14.6) compared with 2.4% (0.5-4.3) with CMT (P = .0008). There were no relevant differences in out-field recurrences (5-year incidence 4.1% [1.7-6.6] vs 6.6% [3.0-10.3], P = .54). There was no grade 4 toxicity observed during IF-RT, and incidence of second primary malignancies was similar in both groups. Conclusions: PET-negative patients of the HD16 study showed no significant toxicity after 20 Gy IF-RT, and we demon-strated that omission of IF-RT resulted in more, particularly local, recurrences. Therefore, consolidation IF-RT should still be considered as standard therapy in this setting. (C) 2021 Elsevier Inc. All rights reserved

Zur Entwicklung von Pflege und Pflegewissenschaft

Schaeffer D, Moers M, Rosenbrock R. Zur Entwicklung von Pflege und Pflegewissenschaft. In: Schwartz FW, Walter U, Siegrist J, et al., eds. Public Health: Gesundheit und Gesundheitswesen. 3., überarbeitete Auflage. München: Urban &amp; Fischer; 2012: 308-310

Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials

To optimize fertility advice in patients with Hodgkin lymphoma (HL) before therapy and during survivorship, information on the impact of chemotherapy is needed. Therefore, we analyzed gonadal functions in survivors of HL

Involved Site Radiotherapy Extends Time to Premature Menopause in Infra-Diaphragmatic Female Hodgkin Lymphoma Patients - An Analysis of GHSG HD14-and HD17-Patients

Introduction Consolidation radiotherapy in intermediate stage Hodgkin ' s lymphoma (HL) has been the standard of care for many years as involved field radiotherapy (IFRT) after chemotherapy. It included initially involved region(s). Based on randomized studies, radiation volumes could be reduced and involved site radiation therapy (ISRT) became the new standard. ISRT includes the initially affected lymph nodes. In young adults suffering from HL, infertility and hypogonadism are major concerns. With regard to these questions, we analyzed the influence of modern radiotherapy concepts such as consolidating ISRT in infradiaphragmatic involvement of HL after polychemotherapy. Patients and Methods Five hundred twelve patients treated within German Hodgkin Study Group (GHSG) HD14 and HD17 trials were evaluated. We analyzed log-adjusted follicle-stimulating-hormone (FSH)- and luteinizing-hormone (LH)-levels of HD14-patients with infradiaphragmatic radiotherapy (IDRT) in comparison with HD14-patients, who had a supradiaphragmatic radiotherapy (SDRT). In a second step, we compared IFRT with ISRT of female HD17 patients regarding the effects on ovarian function and premature menopause. Results We analyzed FSH- and LH-levels of 258 female and 241 male patients, all treated with IFRT. Of these 499 patients, 478 patients had SDRT and 21 patients had IDRT. In a multiple regression model, we could show that log-adjusted FSH (p=0.0006) and LH values (p=0.0127) were significantly higher after IDRT than after SDRT. The effect of IDRT on gonadal function was comparable to two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc). We compared the effect of IFRT with ISRT in thirteen female HD17 patients with infradiaphragmatic (ID) involvement. The mean ovarian dose after ISRT was significantly lower than after IFRT. The calculated proportion of surviving non-growing follicles (NGFs) increased significantly from 11.87% to 24.48% in ISRT compared to IFRT, resulting in a significantly longer calculated time to menopause. The younger the age at therapy, the greater the absolute time gain until menopause. Conclusion Infradiaphragmatic IFRT impairs gonadal function to a similar extent as two cycles of BEACOPPesc. In comparison, the use of ISRT target volume definition significantly reduced radiation dose to the ovaries and significantly extends the time interval from treatment to premature menopause

Volumetric assessment of mediastinal lymphoma masses in Hodgkin lymphoma

The large mediastinal mass (LMM) at initial staging represents a risk factor in Hodgkin lymphoma (HL) and is measured by X-ray. Depending on location of the LMM, different results can occur regardless of the initial lymphoma volume. To assess this risk factor more accurately, we evaluated the method of volumetry in 77 patients of HD13/14 study of the German Hodgkin Study Group. Furthermore, volume calculations based on three or only one diameter, were performed to simplify volume assessment. Inter-rater reliability was good for all methods. The 3-diameter measurement produced larger volumes than volumetric assessment with an intraclass correlation coefficient (ICC) of 0.93, which could be improved to 0.95 by multiplying volumes with a correction factor of 0.86. The 1-dimensional measurement strongly overestimated the volume with an ICC of 0.7. In conclusion, the simplified volume estimation based on 3 largest diameters provides a reliable concept for the staging of HL patients