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Gastric cancer; Metastasectomy; Oligometastasis Cáncer gástrico; Metastasectomía; Oligometástasis Càncer gàstric; Metastasectomia; Oligometàstasi Background Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. Methods In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). Conclusion The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials.

We aimed to evaluate possible factors influencing the long-term survival of teeth after tumor therapy (TT) to the head and neck region with and without radiation. Between January 2019 and January 2020, patients who underwent TT for head and neck cancer and received dental treatment before and after TT at the Department of Prosthetic Dentistry of the Martin Luther University Halle-Wittenberg were enrolled in the study. Clinical examination with assessment of dental status and stimulated salivary flow rate (SFR) was performed and information about disease progression and therapy was retrieved from medical records. Of 118 patients (male: 70.3%; mean age: 63.2 ± 12.4 years), 95 received radiotherapy (RT), and 47 were administered radio-chemotherapy (RCT). The teeth of irradiated patients exhibited a lower 5-year survival probability (74.2%) than those of non-irradiated patients (89.4%). The risk of loss (RL) after RT increased with nicotine use, presence of intraoral defects, reduced SFR, RCT and regarding mandibular teeth, and decreased with crowning following TT. Lower SFR increased the RL even without RT. Consideration of patient’s treatment history, individual risk profile, and clinical findings during the prosthetic planning phase could enable earlier, more targeted dental treatment after TT (e.g., timely crowning).

Background: Early efficacy outcome measures in rectal cancer after total neoadjuvant treatment are increasingly investigated. We examined the prognostic role of pathological complete response (pCR), tumor regression grading (TRG) and neoadjuvant rectal (NAR) score for disease-free survival (DFS) in patients with rectal carcinoma treated within the CAO/ARO/AIO-12 randomized phase 2 trial. Methods: Distribution of pCR, TRG and NAR score was analyzed using the Pearson’s chi-squared test. Univariable analyses were performed using the log-rank test, stratified by treatment arm. Discrimination ability of non-pCR for DFS was assessed by analyzing the ROC curve as a function of time. Results: Of the 311 patients enrolled, 306 patients were evaluable (Arm A:156, Arm B:150). After a median follow-up of 43 months, the 3-year DFS was 73% in both groups (HR, 0.95, 95% CI, 0.63–1.45, p = 0.82). pCR tended to be higher in Arm B (17% vs. 25%, p = 0.086). In both treatment arms, pCR, TRG and NAR were significant prognostic factors for DFS, whereas survival in subgroups defined by pCR, TRG or NAR did not significantly differ between the treatment arms. The discrimination ability of non-pCR for DFS remained constant over time (C-Index 0.58) but was slightly better in Arm B (0.61 vs. 0.56). Conclusion: Although pCR, TRG and NAR were strong prognostic factors for DFS in the CAO/ARO/AIO-12 trial, their value in selecting one TNT approach over another could not be confirmed. Hence, the conclusion of a long-term survival benefit of one treatment arm based on early surrogate endpoints should be stated with caution.

Early efficacy outcome measures in rectal cancer after total neoadjuvant treatment are increasingly investigated. We examined the prognostic role of pathological complete response (pCR), tumor regression grading (TRG) and neoadjuvant rectal (NAR) score for disease-free survival (DFS) in patients with rectal carcinoma treated within the CAO/ARO/AIO-12 randomized phase 2 trial.Distribution of pCR, TRG and NAR score was analyzed using the Pearson's chi-squared test. Univariable analyses were performed using the log-rank test, stratified by treatment arm. Discrimination ability of non-pCR for DFS was assessed by analyzing the ROC curve as a function of time.Of the 311 patients enrolled, 306 patients were evaluable (Arm A:156, Arm B:150). After a median follow-up of 43 months, the 3-year DFS was 73% in both groups (HR, 0.95, 95% CI, 0.63-1.45,Although pCR, TRG and NAR were strong prognostic factors for DFS in the CAO/ARO/AIO-12 trial, their value in selecting one TNT approach over another could not be confirmed. Hence, the conclusion of a long-term survival benefit of one treatment arm based on early surrogate endpoints should be stated with caution.

Oesophageal neoplasm; Oligometastasis; Radiosurgery Neoplàsia esofàgica; Oligometàstasi; Radiocirurgia Neoplasia esofágica; Oligometástasis; Radiocirugía Background Consensus about the definition and treatment of oligometastatic oesophagogastric cancer is lacking. Objective To assess the definition and treatment of oligometastatic oesophagogastric cancer across multidisciplinary tumour boards (MDTs) in Europe. Material and methods European expert centers (n = 49) were requested to discuss 15 real-life cases in their MDT with at least a medical, surgical, and radiation oncologist present. The cases varied in terms of location and number of metastases, histology, timing of detection (i.e. synchronous versus metachronous), primary tumour treatment status, and response to systemic therapy. The primary outcome was the agreement in the definition of oligometastatic disease at diagnosis and after systemic therapy. The secondary outcome was the agreement in treatment strategies. Treatment strategies for oligometastatic disease were categorised into upfront local treatment (i.e. metastasectomy or stereotactic radiotherapy), systemic therapy followed by restaging to consider local treatment or systemic therapy alone. The agreement across MDTs was scored to be either absent/poor (

Highlights • The 3-year disease-free survival of locally-advanced anal carcinoma is about 60%. • Anal carcinoma is considered an immunogenic tumor due to its association with HPV. • The PD-L1 inhibitor durvalumab may synergize with radiochemotherapy. • The RADIANCE trial will test durvalumab with radiochemotherapy in anal carcinoma., Purpose Anal squamous cell carcinomas (ASCC) are increasing in frequency across the developed world. The 3-year disease-free survival (DFS) in patients with locally-advanced disease is approximately 60% after primary radiochemotherapy (RCT). There is a strong rationale for combining immunotherapy with RCT in patients with ASCC due to its association with human papilloma virus (HPV) infection. Methods/design RADIANCE is an investigator initiated, prospective, multicenter, randomized phase II trial testing the addition of Durvalumab, a PD-L1 immune checkpoint inhibitor, to standard RCT in 178 patients with locally advanced ASCC (T2 ≥ 4 cm Nany, cT3-4 and/or cN+). In the control arm, patients will be treated with standard mitomycin C (MMC)/5-fluorouracil (5-FU)-based RCT. Intensity-modulated radiotherapy (IMRT) will be applied as follows: PTV_A (primary tumor) T1-T2

PURPOSE Total neoadjuvant therapy is a new paradigm for rectal cancer treatment. Optimal scheduling of preoperative chemoradiotherapy (CRT) and chemotherapy remains to be established. PATIENTS AND METHODS We conducted a multicenter, randomized, phase II trial using a pick-the-winner design on the basis of the hypothesis of an increased pathologic complete response (pCR) of 25% after total neoadjuvant therapy compared with standard 15% after preoperative CRT. Patients with stage II or III rectal cancer were assigned to group A for induction chemotherapy using three cycles of fluorouracil, leucovorin, and oxaliplatin before fluorouracil/oxaliplatin CRT (50.4 Gy) or to group B for consolidation chemotherapy after CRT. Secondary end points included toxicity, compliance, and surgical morbidity. RESULTS Of the 311 patients enrolled, 306 patients were evaluable (156 in group A and 150 in group B). CRT-related grade 3 or 4 toxicity was lower (37% v 27%) and compliance with CRT higher in group B (91%, 78%, and 76% v 97%, 87%, and 93% received full-dose radiotherapy, concomitant fluorouracil, and concomitant oxaliplatin in groups A and B, respectively); 92% versus 85% completed all induction/consolidation chemotherapy cycles, respectively. The longer interval between completion of CRT and surgery in group B (median 90 v 45 days in group A) did not increase surgical morbidity. A pCR in the intention-to-treat population was achieved in 17% in group A and in 25% in group B. Thus, only group B ( P < .001), but not group A ( P = .210), fulfilled the predefined statistical hypothesis. CONCLUSION Up-front CRT followed by chemotherapy resulted in better compliance with CRT but worse compliance with chemotherapy compared with group A. Long-term follow-up will assess whether improved pCR in group B translates to better oncologic outcome.

During prosthetic rehabilitation after tumor therapy (TT) in the head and neck region, the dentist must assess whether the prognosis of the remaining teeth is sufficiently good or whether implants should be used to anchor dentures. Thus, the aim of the present study was to compare the survival rate of teeth and implants after TT and to evaluate factors potentially influencing implant survival. One hundred fifteen patients (male: 70.3%; mean age: 63.2 ± 12.4 years) having received dental treatment before and after TT at the Martin Luther University Halle-Wittenberg were enrolled in the study. Clinical examination including assessment of dental status and stimulated salivary flow rate was performed. Information about disease progression and therapy was retrieved from medical records. After TT, from a total of 1262 teeth, 27.2% had to be extracted. Of 308 implants inserted after TT, 7.0% were lost. Teeth exhibited lower 5-year survival probability (76.8%) than implants (89.9%; p = 0.001). The risk of loss (RL) of implants increased with age, nicotine use, intraoral defects, and RCT. Radiotherapy did not independently increase the RL. Thus, implants seem to be a reliable treatment option in case of progressive tooth decay after TT, particularly after RT.

Due to the broad spectrum of individual functionalities, current hospital information systems in most cases do not offer quick information access or proper assistance in information assessment. This results in extensive use of raw value representations and the need to process and evaluate those cognitively through the physician. This can result in an error-prone and ineffective process, especially in complex and chronic treatment scenarios. With an example scenario of laboratory value assessment in head and neck oncology, we have evaluated the requirements for extensive support of case interpretation through the conduction of a Delphi study including five medical experts with different levels of expertise. Based on the results, we propose a solution with integrated HL7 FHIR compliant clinical decision-support functionality through a set of integrated rules from relevant clinical practice guidelines. Furthermore, we introduce the implementation of a dedicated application that allows for the definition of custom laboratory value evaluation rules to enable automated and patientindividual value interpretation.

Mixed reality (MR) represents a new evolution in technological development that combines both virtual reality (VR) and augmented reality (AR) to create a blend of the physical and digital worlds. However, the potential role of MR in preoperative diagnostics in oral and maxillofacial surgery has not been scientifically investigated and remains generally unclear. This article presents a workflow that integrated MR in its scheme. It also evaluates the potential benefit of MR compared with its predecessors, VR and AR.MR technology was used to plan the surgical treatment of a clinical case with an extensive tumor of the left maxilla. A workflow proposal incorporating both the surgeon and radiation oncologist is presented based on this experience. A total of 10 examiners rated the usability and applicability of MR for daily routines.MR showed good results during preoperative planning for a surgically extensive case in terms of displaying 3D structures and enhancing the physical and virtual interactions among the examiners. Previously described drawbacks of other VR/AR applications such as nausea and motion sickness were not observed with MR. However, MR seems to lack intraoperative usability, which is a drawback.MR shows great potential in improving the preoperative assessment of 3D DICOM datasets and thus facilitating diagnostic measures. However, further improvements should be made to implement an MR workflow and incorporate it into the clinical treatment planning tree.

Purpose To investigate the efficacy and toxicity of cetuximab when added to radiochemotherapy for unresectable esophageal cancer. Methods This randomized phase 2 trial (clinicaltrials.gov, identifier NCT01787006) compared radiochemotherapy plus cetuximab (arm A) to radiochemotherapy (arm B) for unresectable esophageal cancer. Primary objective was 2‑year overall survival (OS). Arm A was considered insufficiently active if 2‑year OS was ≤40% (null hypothesis = H0), and promising if the lower limit of the 95% confidence interval was >45%. If that lower limit was >40%, H0 was rejected. Secondary objectives included progression-free survival (PFS), locoregional control (LC), metastases-free survival (MFS), response, and toxicity. The study was terminated early after 74 patients; 68 patients were evaluable. Results Two-year OS was 71% in arm A (95% CI: 55–87%) vs. 53% in arm B (95% CI: 36–71%); H0 was rejected. Median OS was 49.1 vs. 24.1 months (p = 0.147). Hazard ratio (HR) for death was 0.60 (95% CI: 0.30–1.21). At 2 years, PFS was 56% vs. 44%, LC 84% vs. 72%, and MFS 74% vs. 54%. HRs were 0.51 (0.25–1.04) for progression, 0.43 (0.13–1.40) for locoregional failure, and 0.43 (0.17–1.05) for distant metastasis. Overall response was 81% vs. 69% (p = 0.262). Twenty-six and 27 patients, respectively, experienced at least one toxicity grade ≥3 (p = 0.573). A significant difference was found for grade ≥3 allergic reactions (12.5% vs. 0%, p = 0.044). Conclusion Given the limitations of this trial, radiochemotherapy plus cetuximab was feasible. There was a trend towards improved PFS and MFS. Larger studies are required to better define the role of cetuximab for unresectable esophageal cancer.

Background Recent advances in diagnostic methods and in radiotherapy now increasingly enable repeat radiotherapy with curative intent for the treatment of previously irradiated lesions. In this review, we present data on oncological outcomes and on acute and late sequelae, as far as these are currently known, in patients with head and neck tumors (HNT) or prostate cancer (PCa) who underwent repeat radiotherapy after prior radiotherapy with curative intent. Methods This review is based on clinical series with over 20 patients that were published between May 1998 and April 2018 (HNT) or between October 1998 and October 2018 (PCa) and were retrieved by a search in the PubMed database. Results Most of the clinical series retrieved were retrospective and uncontrolled. There were 16 studies that included 2678 patients with recurrent head and neck tumors, and 8 that included 245 patients with recurrent prostate cancer. In patients with squamous cell carcinoma of the head and neck, intensity-modulated radio - therapy (IMRT) and stereotactic body radiotherapy (SBRT) yielded three-year survival rates of 47-57% but also produced substantial acute and late adverse effects. Most of the studies concerning recurrent PCa involved small patient groups. In these studies, repeat radiotherapy with SBRT yielded tumor control rates of 40-80% after 11-24 months of follow-up, with only mild acute toxicity. Conclusion Although no comparative studies are available, it seems that modern external beam radiotherapy techniques can be used for repeat radiotherapy of locally recurrent head and neck tumors with curative intent after careful patient selection. Repeat radiotherapy of PCa must still be considered experimental, but initial results from small-scale trials are encouraging. The long-term adverse effects cannot yet be accessed. Patients should be selected by an interdisciplinary tumor board. This type of treatment is generally carried out in a specialized center.

Importance Total neoadjuvant therapy has been increasingly adopted for multimodal rectal cancer treatment. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy needs to be established. Objective To report the long-term results of the secondary end points prespecified in the Randomized Phase 2 Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy (CAO/ARO/AIO-12 trial) for Locally Advanced Rectal Cancer. Design, Setting, and Participants This secondary analysis of a randomized clinical trial included 311 patients who were recruited from the accrued CAO/ARO/AIO-12 trial population from June 15, 2015, to January 31, 2018, from 18 centers in Germany. Patients with cT3-4 and/or node-positive rectal adenocarcinoma were included in the analysis. Data were analyzed from June 15, 2015, to January 31, 2018. The follow-up analysis was conducted between January 31, 2018, and November 30, 2020. Interventions Patients were randomly assigned to group A for 3 cycles of fluorouracil, leucovorin, and oxaliplatin before fluorouracil/oxaliplatin CRT (50.4 Gy), or to group B for CRT before chemotherapy. Total mesorectal excision was scheduled on day 123 after the start of total neoadjuvant therapy in both groups. Main Outcomes and Measures The end points assessed in this secondary analysis included long-term oncologic outcomes, chronic toxicity, patient-reported outcome measures for global health status (GHS) and quality of life (QoL), and the Wexner stool incontinence score. Results Of the 311 patients enrolled, 306 were evaluable, including 156 in group A (mean [SD] age, 60 [11] years; 106 men [68%]) and 150 in group B (mean [SD] age, 62 [10] years; 100 men [67%]). After a median follow-up of 43 months (range, 35-60 months), the 3-year disease-free survival was 73% in both groups (hazard ratio, 0.95; 95% CI, 0.63-1.45,P = .82); the 3-year cumulative incidence of locoregional recurrence (6% vs 5%,P = .67) and distant metastases (18% vs 16%,P = .52) were not significantly different. Chronic toxicity grade 3 to 4 occurred in 10 of 85 patients (11.8%) in group A and 8 of 66 patients (9.9%) in group B at 3 years. The GHS/QoL score decreased after total mesorectal excision but returned to pretreatment levels 1 year after randomization with no difference between the groups. Stool incontinence deteriorated 1 year after randomization in both groups and only improved slightly at 3 years, but never reached baseline levels. Conclusions and Relevance This secondary analysis of a randomized clinical trial showed that CRT followed by chemotherapy resulted in higher pathological complete response without compromising disease-free survival, toxicity, QoL, or stool incontinence and is thus proposed as the preferred total neoadjuvant therapy sequence if organ preservation is a priority. Trial Registration ClinicalTrials.gov identifier:NCT02363374

Induction chemotherapy (ICT) with docetaxel, cisplatin and fluorouracil (TPF) followed by radiotherapy is an effective treatment option for locally advanced head and neck cancer. This phase II study investigated the effectivity of a split-dose TPF ICT before surgery for locally advanced resectable (stage III/IVA) oral and oropharyngeal cancer.Patients received TPF split on two dosages on days 1 and 8 per cycle (30 mg/m2 docetaxel, 40 mg/m2 cisplatin, 2000 mg/m2 fluorouracil per week). Responders (reduction tumor volume ≥30% after first cycle) received three 3-week cycles and non-responders only one cycle before surgery and postoperative radio(chemo)therapy (RCT). The primary endpoint was progression-free survival rate after 24 months. Secondary endpoints were amongst others overall survival, histopathological response to ICT, toxicity, quality of life and swallowing function.Fifty-four patients (91% stage IVA, 87% male, 72% oropharyngeal cancer, 70% responders) were eligible for a per-protocol analysis. The progression-free survival rate after 24 months was 88.5% for responders and 60.6% for non-responders (P = 0.005). The overall survival rate after 24 months was 97.3% for responders and 73.7% for non-responders (P = 0.032). The rate of histopathological complete remission of the primary tumor was higher in responders (P = 0.015). High-risk classification for postoperative RCT was lower in responders (P 0.0001). The most common grade 3+ adverse event was neutropenia in 26% of patients during ICT and mucositis in 13% during postoperative RCT. During treatment and follow-up quality of life and swallowing function was not different between responders and non-responders.Patients with oral and oropharyngeal cancer responding to split-dose TPF before surgery and postoperative RCT show good oncological results. The tri-modal treatment regime was well tolerated. ICT using tumor response as criterion for duration of ICT before surgery of oral and oropharyngeal cancer merits additional investigation in a phase III study.NCT01108042.

Cetuximab (CET) is a potent inhibitor of the epidermal growth factor receptor and has been shown to have activity in squamous cell carcinoma of the head and neck (SCCHN). We conducted a single-arm phase II trial of a combination therapy comprising cisplatin (CIS), CET and hyperfractionated accelerated radiotherapy (HART). Patients with UICC stage III or IVA/B, M0 SCCHN were enrolled and treated with an initial dose of CET (400 mg/m2) and then with a weekly dosage of 250 mg/m2 during HART. HART was started with a prescribed dosage of 2.0 Gy per day for 3 weeks, followed by 1.4 Gy twice daily to a total dose of 70.6 Gy to the gross tumour volume. CIS (40 mg/m2) was administered weekly (days 1, 8, 15, 22, 29 and 36). The primary objective of the phase II study was to determine the 2‑year progression-free survival (PFS). Between November 2007 and November 2010, a total of 74 patients were enrolled in the study, of whom 65 were evaluable (83% were men). Median age was 56 years (range 37–69 years). An Oropharyngeal primary tumour was diagnosed in 49%, T4a,b in 65% and N2/3 in 96% of the patients. Of these patients, 85% were smokers or ex-smokers. Complete remission (CR) was observed in 23 patients (35%). The most common toxicity grade was ≥3, including mucositis (58%) and dysphagia (52%). The 2‑ and 5‑year overall survival rates were 64 and 41%, the 2‑ and 5‑year PFS rates were 45 and 32%, and the 2‑ and 5‑year locoregional control rates were 47 and 33%, respectively. The combination of weekly CIS with HART plus CET is a feasible regimen for these unfavourable smoking-induced cancers. However, the parallel US study (RTOG 0522) showed no advantage of the enhanced triple therapy compared to chemoradiotherapy alone.

The aim of this study was to analyze the influence of dental treatment on the development of osteoradionecrosis (ORN) of the jaw. This study included the data of 776 patients who underwent 3D-CRT or IMRT because of head and neck cancer. Sex, dental status before and after radiotherapy (RT), tumor site, bone surgery during tumor operation, concomitant chemotherapy, and the development of an advanced ORN were documented for each patient. The patients’ dentitions before and after RT were classified into four groups with regard to the number and localization of the remaining teeth. Differences between the patients with ORN and patients without ORN with regard to the teeth’s condition before and after RT, and with regard to the extent of dental treatment were determined descriptively. Cox proportional hazards regression to study the association between dentition and the development of ORN. The extent of dental treatment in patients with and without ORN did not differ in a clinically relevant way. The highest risk of developing ORN was observed in patients who had undergone primary bone surgery during the tumor operation (HR = 5.58, 95%CI 2.91–10.7) and patients who had a tumor in the oral cavity (HR = 4.84, 95%CI 1.37–17.11). Based on the results of this study, tumor localization and its required treatment are prognostic factors for the development of ORN. After implementing a consequent dental treatment scheme, no influence of dentition on the risk of developing ORN could be demonstrated. Patients with a lower risk could prospectively benefit from a more moderate dental treatment scheme.

BACKGROUND Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinomas (OPSCCs) demonstrate superior outcome compared with HPV-negative OPSCCs. The eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, lymph node, metastasis (TNM) classification (TNM 2017) modifies OPSCC staging based on p16 positivity as a surrogate for HPV-driven disease. In p16-negative OPSCCs, lymph node (N) categories include extracapsular/extranodal extension (ECE); and, in p16-positive OPSCCs, N categories are based on the number of positive neck lymph nodes omitting ECE status. The objective of the current study was to assess the prognostic impact of positive ECE status and the detection of HPV16 DNA in patients with p16-positive OPSCC. METHODS In a cohort of 92 patients with p16-positive, lymph node (N)-positive (stage III-IVB) OPSCC who underwent surgery and neck dissection, allowing for a pathologic examination of positive lymph nodes, 66 of 92 patients (71.4%) were p16-positive/HPV16 DNA-positive, 62 of 92 (67%) were ECE-positive, and 45 of 62 (72.6%) were ECE-positive, p16-positive, and HPV16 DNA-positive. Differences in outcome were assessed using Kaplan-Meier plots and Cox proportional hazard regression (CoxR) for tumor-specific survival and overall survival (OS). RESULTS The mean numbers of positive lymph nodes in ECE-positive patients (5.0 positive lymph nodes; 95% CI, 3.8-6.4 positive lymph nodes) and ECE-negative patients (2.4 positive lymph nodes; 95% CI, 1.8-2.9 positive lymph nodes) were different (P = .0007). ECE affected OS and tumor-specific survival in p16-positive patients (P = .007 and P = .047, respectively) and in p16-positive/HPV16 DNA-positive patients (P = .013 and P = .026, respectively). Related to the unequal distributions of ECE-positive/HPV16 DNA-negative tumors, the TNM 2017 failed to discriminate OS in patients with UICC stage I, II, and III disease (mean OS, 54.5, 73.4, and 45 months, respectively; median OS, 64.7 months, not reached, and 41.1 months, respectively). According to a univariate CoxR, the presence of ECE predicted impaired OS in patients with p16-positive OPSCC (hazard ratio, 3.40; 95% CI, 1.17-9.89; P = .025) and even greater impaired OS in those with p16-positive/HPV16 DNA-positive OPSCC (HR, 8.64; 95% CI, 1.12-66.40; P = .038). Multivariate CoxR confirmed ECE and HPV16 DNA detection as independent predictors. CONCLUSIONS ECE and HPV16 DNA status should be included in the prognostic staging of patients with p16-positive OPSCC because several lines of evidence demonstrate their impact on survival.

In the locoregional advanced group of larynx and hypopharyngeal squamous cell carcinomas (LHSCC), there are two kinds of patients: those who are candidates for functional larynx organ preservation (LP) by avoiding ablative surgery and those who are not. Currently, the distinction between them is depending on the patient's needs and desires, the experience and recommendation of the surgeon, the philosophy of the institution and others. The milestone VA trial established non-surgical LP in advanced LHSCC utilizing induction-chemotherapy (IC) with PF (cisplatin, P plus 5-fluorouracil, F) followed by irradiation (IC+RT) as appropriate alternative treatment to total laryngectomy (TL) already in the 1990s. Even thou the VA trial's findings were verified by the EORTC 24891 trial we have an ongoing debate about the best protocol balancing survival and laryngectomy-free survival (LFS) with acceptable late toxicity and good functional outcome. In advanced LHSCC without surgical options preserving the larynx, only IC+RT and primary concurrent chemo-radiotherapy (CRT) are accepted treatment options aiming to preserve a functional larynx. In the US, cisplatin-based CRT is still recommended as best protocol to achieve cure of the disease and LP. But current views on long term survival with functional organ preservation and still high failure rates are addressing the need of better selection of patients which will be discussed as follows taking the current debate in literature and in particular the recently published data of the DeLOS-II trial in consideration.

Background Older patients are vulnerable to chemotherapy-related toxicity (CRT). Therefore we evaluated screening tools in their power to predict CRT. Methods Patients with cancer aged ≥65 years completed three screening questionnaires (G8, optimised G8 and Cancer and Ageing Research Group (CARG). Additionally, Comprehensive geriatric assessment (CGA) for verification of supportive care needs was undertaken on patients with impaired G8 scores. During chemotherapy treatment patients were assessed, capturing grade 0–5 CRT as defined by NCI CTCAE 4. Results 104 patients with non-haematological cancers were included at three study sites. Median age was 73 years (range 65–85). Onco-geriatric screening detected 74% as impaired using G8 and optimised G8 questionnaires and 86% using CARG screening. Grade 3–5 toxicity affected 64.4% of all patients. G8 (OR 0.3 95% CI [0.1;1.0]) and optimised G8 (OR 0.4 95% CI [0.1; 1.5]) did not reliably predict CRT, whereas screening with CARG demonstrated a strong prediction of severe CRT: OR 4.2, 95% CI [1.1, 15.9]. CGA was undertaken on 66 patients, revealing deficiencies in nutritional (83%) and functional-status (54%) and occurrence of relevant comorbidity (53%). Conclusion The CARG tool could be useful for predicting CRT. CGA showed clinically relevant supportive care needs in patients with a positive G8 screening.

To analyze the influence of dental treatment on oral health-related quality of life (OHRQoL) in head and neck cancer patients. This study included the data of 116 patients who underwent radiotherapy (RT) because of head and neck cancer. For each patient, the variables age, sex, tumor site, irradiation technique, dose on the spared parotid gland, concomitant chemotherapy, and denture status were documented. OHRQoL was determined using the OHIP-G14 questionnaire. Patients were divided into subgroups according to denture status: none or fixed partial dentures (none/FPD), removable partial dentures (RPD), and full dentures (CD). OHIP summary scores were determined and tested for clinical relevant differences with respect to the different variables. The association between OHRQol and the variables was assessed using linear regression. No clinically relevant influence on OHRQoL was found for gender, irradiation technique, and chemotherapy. Patients with tumors located in the oral cavity had a significantly higher OHIP score than patients with other tumor sites (p

Background The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). Patients and methods Treatment-naive patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m2/day 1, 5-FU (F) 750 mg/m2/day days 1–5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with ≥30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. Results Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed IC+RT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. Conclusions Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. Clinical trial information NCT00508664.

In recent years, camptocormia and dropped head syndrome (DHS) have gained attention as particular forms of movement disorders. Camptocormia presents with involuntary forward flexion of the thoracolumbar spine that typically increases during walking or standing and may severely impede walking ability. DHS is characterized by weakness of the neck extensors and a consecutive inability to extend the neck; in severe cases the head is fixed in a “chin to chest position.” Many diseases may underlie these conditions, and there have been some reports about radiation-induced camptocormia and DHS. A PubMed search with the keywords “camptocormia,” “dropped head syndrome,” “radiation-induced myopathy,” “radiation-induced neuropathy,” and “radiation-induced movement disorder” was carried out to better characterize radiation-induced movement disorders and the radiation techniques involved. In addition, the case of a patient developing camptocormia 23 years after radiation therapy of a non-Hodgkin’s lymphoma of the abdomen is described. In total, nine case series of radiation-induced DHS (n = 45 patients) and—including our case—three case reports (n = 3 patients) about radiogenic camptocormia were retrieved. Most cases (40/45 patients) occurred less than 15 years after radiotherapy involving extended fields for Hodgkin’s disease. The use of wide radiation fields including many spinal segments with paraspinal muscles may lead to radiation-induced movement disorders. If paraspinal muscles and the thoracolumbar spine are involved, the clinical presentation can be that of camptocormia. DHS may result if there is involvement of the cervical spine. To prevent these disorders, sparing of the spine and paraspinal muscles is desirable.

Die Behandlung lokal fortgeschrittener Adenokarzinome des Osophagus und des osophagogastralen Ubergangs wurde uber Jahrzehnte kontrovers diskutiert. Die chirurgische Resektion wurde als die einzige kurative Behandlungsmodalitat angesehen. Kontrollierte klinische Studien konnten belegen, dass neoadjuvante Therapiekonzepte zur Verbesserung der R0-Resektionsrate, Senkung der systemischen Rezidivrate und zur Verbesserung der Gesamtprognose fuhren. Die neoadjuvante Chemotherapie wurde mittlerweile fur die Behandlung der Tumorstadien cT3 und resektabel cT4 als Standard etabliert. Die Radiochemotherapie kann eine alternative Behandlungsoption hierfur sein. Trotz der Fortschritte erreicht man bei etwa 30–60 % der Patienten keine langfristige Tumorkontrolle. Wirksamere Behandlungsregime werden benotigt. Um bessere Ergebnisse zu erreichen, sollte die kurative Therapie des Osophaguskarzinoms an Zentren mit interdisziplinarer Zusammenarbeit, Qualitatssicherung und Erfahrung erfolgen. Aktuelle Forschungsschwerpunkte richten sich auf personalisierte Therapien sowie die Erforschung pradiktiver und prognostischer Parameter.

(1) Background: About 15% of the patients undergoing neoadjuvant chemoradiation for locally advanced rectal cancer exhibit pathological complete response (pCR). The surgical approach is associated with major risks as well as a potential negative impact on quality of life and has been questioned in the past. Still, there is no evidence of a reliable clinical or radiological surrogate marker for pCR. This study aims to replicate previously reported response predictions on the basis of non-contrast CT scans on an independent patient cohort. (2) Methods: A total of 169 consecutive patients (126 males, 43 females) that underwent neoadjuvant chemoradiation and consecutive total mesorectal excision were included. The solid tumors were segmented on CT scans acquired on the same scanner for treatment planning. To quantify intratumoral 3D spatial heterogeneity, 1819 radiomics parameters were derived per case. Feature selection and algorithmic modeling were performed to classify pCR vs. non-pCR cases. A random forest model was trained on the dataset using 4-fold cross-validation. (3) Results: The model achieved an accuracy of 87%, higher than previously reported. Correction for the imbalanced distribution of pCR and non-PCR cases (13% and 87% respectively) was applied, yielding a balanced accuracy score of 0.5%. An additional experiment to classify a computer-generated random data sample using the same model led to comparable results. (4) Conclusions: There is no evidence of added value of a radiomics model based on on-contrast CT scans for prediction of pCR in rectal cancer. The imbalance of the target variable could be identified as a key issue, leading to a biased model and optimistic predictions., publishedVersion

BACKGROUND In patients with head and neck and esophageal tumors, nutritional status may deteriorate during concurrent chemoradiotherapy (CRT). The aim of this study was to investigate the influence of enteral nutrition enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on body composition and nutritional and functional status. METHODS In a controlled, randomized, prospective, double-blind, multicenter study, 111 patients with head and neck and esophageal cancer undergoing concurrent CRT received either an enteral standard nutrition (control group) or disease-specific enteral nutrition Supportan®-containing EPA+DHA (experimental group) via percutaneous endoscopic gastrostomy. The primary endpoint was the change of body cell mass (BCM) following CRT at weeks 7 and 14 compared with the baseline value. Secondary endpoints were additional parameters of body composition, anthropometric parameters, and nutritional and functional status. RESULTS The primary endpoint of the study, improvement in BCM, reached borderline statistical significance. Following CRT, patients with experimental nutrition lost only 0.82 ± 0.64 kg of BCM compared with 2.82 ± 0.77 kg in the control group (P = .055). The objectively measured nutritional parameters, such as body weight and fat-free mass, showed a tendency toward improvement, but the differences were not significant. The subjective parameters, in particular the Kondrup score (P = .0165) and the subjective global assessment score (P = .0065) after follow-up improved significantly in the experimental group, compared with the control group. Both enteral regimens were safe and well tolerated. CONCLUSION Enteral nutrition with EPA and DHA may be advantageous in patients with head and neck or esophageal cancer by improving parameters of nutritional and functional status during CRT. Cancer 2013;119:3343–53. © 2013 American Cancer Society.

Head and neck squamous cell carcinoma is the 6th most malignant tumor entity worldwide and has exhibited a 5-year mortality of approximately 50% for the last fifty years. For the therapy monitoring and successful management of this tumor entity new and easily accessible biomarkers are greatly needed. The aim of the study was to determine whether and to what extent microRNAs, a class of small regulatory RNAs, are detectable in saliva post-radiation therapy. The expression and feasibility as therapy monitoring marker of the microRNAs were analyzed by RT-qPCR in 83 saliva samples from 33 patients collected at several time points pre-, during and post-radiotherapy treatment. Ten head and neck squamous cell carcinoma- or radiation-associated microRNAs (miR-93, miR-125a, miR-142-3p, miR-200a, miR-203, miR-213, let-7a, let-7b, let-7g and let-7i) were analyzed. All were detectable to a different extent in the saliva of the patients. miR-93 and miR-200a were significantly higher expressed 12 months post-radiotherapy than at baseline (p=0.047 and p=0.036). These results point towards miR-93 and miR-200a as biomarkers for the treatment monitoring post-radiation of head and neck squamous cell carcinoma.

OA gold Introduction: To identify potential risk factors for the development of jaw osteoradionecrosis (ORN) after 3D-conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) among patients with newly diagnosed head and neck cancer. Material and methods: This study included 776 patients who underwent 3D-CRT or IMRT for head and neck cancer at the Department of Radiotherapy at the University Hospital Halle-Wittenberg between 2003 and 2013. Sex, dental status prior to radiotherapy, tumor site, bone surgery during tumor resection, concomitant chemotherapy, and the development of advanced ORN were documented for each patient. ORN was classified as grade 3, 4, or 5 according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer classification or grade 3 or 4 according to the late effects in normal tissues/subjective, objective, management, and analytic scale. The cumulative incidence of ORN was estimated. Cox regression analysis was used to identify prognostic risk factors for the development of ORN. Results: Fifty-one patients developed advanced ORN (relative frequency 6.6 %, cumulative incidence 12.4 %). The highest risk was found in patients who had undergone primary bone surgery during tumor resection (hazard ratio [HR] = 5.87; 95 % confidence interval [CI]: 3.09–11.19) and in patients with tumors located in the oral cavity (HR = 4.69; 95 % CI: 1.33–16.52). Sex, dentition (dentulous vs. edentulous), and chemotherapy had no clinically relevant influence. Discussion and conclusion: In contrast to most previous studies, we noted a low cumulative incidence of advanced ORN. Patients with tumors located in the oral cavity and those who undergo bone surgery during tumor resection prior to RT may be considered a high-risk group for the development of ORN.

The aim of the present study was to evaluate whether radiation damage on dental hard tissue depends on the mean irradiation dose the spared parotid gland is subjected to or on stimulated whole salivary flow rate.Between June 2002 and October 2008, 70 patients with neck and cancer curatively irradiated were included in this study. All patients underwent dental treatment referring to the guidelines and recommendations of the German Society of Dental, Oral and Craniomandibular Sciences prior, during, and after radiotherapy (RT). During the follow-up period of 24 months, damages on dental hard tissues were classified according to the RTOG/EORTC guidelines. The mean doses (D(mean)) during spared parotid gland RT were determined. Stimulated whole saliva secretion flow rates (SFR) were measured before RT and 1, 6, 12, 24 months after RT.Thirty patients showed no carious lesions (group A), 18 patients developed sporadic carious lesions (group B), and 22 patients developed general carious lesions (group C). Group A patients received a D mean of 21.2 ± 11.04 Gy. Group B patients received a D(mean) of 26.5 ± 11.59 Gy and group C patients received a D(mean) of 33.9 ± 9.93 Gy, respectively. The D(mean) of group A was significantly lower than the D(mean) of group C (p 0.001). Additionally, the mean SFR 6 months after RT of group A was significantly higher than the mean SFR of group C (p 0.01).Irradiation damage on dental hard tissue correlates with increased mean irradiation doses as well as decreased salivary flow rates.Parotid gland sparing resulting in a dose below 20 Gy reduces radiation damage on dental hard tissues, and therefore, the dose may act as a predictor for the damage to be expected.

Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.Received: June 16, 2010; accepted: February 4, 2011Published Online: April 26, 2011Background: The aim of this study was to analyze the prognostic importance of extracapsular nodal spread (ECS) in patients with locally advanced squamous cell carcinoma (SCC) of the oral cavity or oropharynx, and the impact of adjuvant low single dose cisplatin-based radiochemotherapy on distant metastases-free survival (DMFS).Patients and Methods: The study population was selected from 195 patients with high-risk oral cavity or oropharyngeal can-cer, who had either adjuvant radiotherapy (RT) or radiochemotherapy (RCT) between January 1, 1997 and December 31, 2006, at the University Clinic of Radiation Oncology of the Martin-Luther-University Halle- Wittenberg. A total of 42 matched pairs of patients with UICC stage III–IVa,b disease were analyzed. The patients were matched (one to one) according to tumor site, sex, T stage, N stage, ECS, resection margin status, and Karnofsky performance status. To analyze the correlation between the treatment modality (RT vs. RCT) and the impact of ECS on DMFS, the Cox proportional hazard model was used. Survival rates were calculated using the Kaplan–Meier method.Results: There was a strong correlation between the degree of nodal involvement and ECS (pN1: 33%; pN2b: 45%; pN2c: 71%). Moreover, the 5-year locoregional control rates (LC) in patients with ECS were 76% vs. 63% (n.s.) for RT and RCT, respectively. However, for patients without ECS, the LC was more favorable after RCT (RT vs. RCT: 62% vs. 88%, p < 0.05). DMFS again was better after RT, and this observation was independent of the presence or absence of ECS. Finally, in multivariate analyses, the presence of ECS significantly decreased the DMFS (p = 0.04, hazard ratio (HR) 2.64). Conclusions: Patients with ECS have an increased risk of distant metastases. Adjuvant low single dose cisplatin-based concur-rent chemotherapy seems to have no influence on occult microscopic systemic disease.

Purpose To determine the influence of concomitant radiochemotherapy with cisplatin on parotid gland tissue complication probability. Methods and Materials Patients treated with either radiotherapy ( n = 61) or concomitant radiochemotherapy with cisplatin ( n = 36) for head-and-neck cancer were prospectively evaluated. The dose and volume distributions of the parotid glands were noted in dose–volume histograms. Stimulated salivary flow rates were measured before, during the 2 nd and 6 th weeks and at 4 weeks and 6 months after the treatment. The data were fit using the normal tissue complication probability model of Lyman. Complication was defined as a reduction of the salivary flow rate to less than 25% of the pretreatment flow rate. Results The normal tissue complication probability model parameter TD 50 (the dose leading to a complication probability of 50%) was found to be 32.2 Gy at 4 weeks and 32.1 Gy at 6 months for concomitant radiochemotherapy and 41.1 Gy at 4 weeks and 39.6 Gy at 6 months for radiotherapy. The tolerated dose for concomitant radiochemotherapy was at least 7 to 8 Gy lower than for radiotherapy alone at TD 50 . Conclusions In this study, the concomitant radiochemotherapy tended to cause a higher probability of parotid gland tissue damage. Advanced radiotherapy planning approaches such as intensity-modulated radiotherapy may be partiticularly important for parotid sparing in radiochemotherapy because of cisplatin-related increased radiosensitivity of glands.

Transurethral resection of bladder tumor (TUR-BT) and radiochemotherapy with cisplatin achieve high rates of bladder preservation and survival figures identical to radical cystectomy in muscle-invasive bladder cancers. The authors have investigated the potential use of paclitaxel in a radiochemotherapy protocol for patients with inoperable bladder carcinomas and mainly contraindications to cisplatin. Between October 1997 to August 2004, 42 patients (median age 71 years) suffering from muscle-invasive (n = 32) or recurrent (n = 10) bladder cancers were treated with a paclitaxel-containing radiochemotherapy (paclitaxel 25–35 mg/m2 twice weekly) after TUR-BT (R0/1/2/x in n = 18/4/14/3) or cystectomy with residual tumor (n = 3). Five patients received additional cisplatin. Radiation treatment was administered to a total dose of 45–60 Gy. 76.2% completed the planned regimen. Adaptations of treatment were mainly required due to diarrhea. Grade 3/4 toxicities occurred in 15/1 patients. Severe renal toxicities did not occur. 28 patients underwent restaging TUR-BT 6 weeks after radiochemotherapy (complete remission/partial remission/progressive disease: n = 24/3/1). Three patients developed a local recurrence and four distant metastases. Seven patients died from tumor, six of other reasons. Radiochemotherapy with paclitaxel was feasible and this bladder approach needs further investigation to evaluate whether paclitaxel could become a substitute for cisplatin.

Purpose: The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO 2 ), the hypoxia-related markers hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated. Methods and Materials: Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1α, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO 2 ), HIF-1α and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied. Results: Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level ( p = 0.02), high HIF-1α expression ( p = 0.02), and high serum vascular endothelial growth factor level ( p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO 2 correlated significantly with the OPN expression ( p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1α or CA IX was associated with a 4.1-fold increased risk of death ( p = 0.02) compared with negativity of all three markers. Conclusion: Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1α, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found.

In dieser Arbeit sollte unter Ausnutzung der Vorzuge der modernen 3D-Planung eine Verbesserung der Bestrahlungstechnik von Kopf-Hals-Tumoren im Hinblick auf die Parotisschonung erreicht werden. Fur die Untersuchung fand der 3D-Datensatz eines Patienten mit einem Tonsillenkarzinom im UICC-Stadium IVA mit der Tumorformel pT4a pN2b M0 R0 Verwendung. In den CT-Scans (Schichtdicke 5 mm) wurden das Planungszielvolumen (PTV), das Boostvolumen sowie beide Parotiden eingezeichnet. Die Plane wurden fur drei verschiedene Techniken berechnet (50 Gy im PTV und 64 Gy im Boost, 2 Gy Einzeldosis). Technik 1 (T1) war eine opponierende Photonen/Elektronen-Technik, Technik 2 (T2) eine Stehfeld/Pendel-Technik und Technik 3 (T3) eine Kombination von komplexer Stehfeld- und Pendeltechnik. Ausgewertet wurden die Summationsdosen Dmin, Dmax, Dmean fur PTV, Boost und die Parotiden mit zusatzlicher Erhebung des Zeitaufwands fur die Planerstellung. Fur alle Techniken waren die errechneten Dosen im PTV (Dmin 5,6 ± 0,1, Dmax 73,7 ± 0,1 und Dmean 57,9 ± 0,5 Gy) und im Boost (Dmin 46,9 ± 1,5, Dmax 73,8 ± 0,12 und Dmean 65,8 ± 0,9 Gy) gleich. Die Techniken unterschieden sich signifikant zugunsten T3 in Hinsicht auf die ipsilaterale Parotis bei Dmin (T1 = 47,4, T2 = 50,6 und T3 = 38,4 Gy) sowie in der kontralateralen Parotis mit Dmin (T1 = 42,1, T2 = 44,2 und T3 = 17,8 Gy) und Dmean (T1 = 51,3, T2 = 52,8 und T3 = 32,6 Gy). Die gemessenen Planungszeiten lagen fur T1 bei 90, fur T2 bei 60 und fur T3 bei 90 min. Die Kombination von komplexer Stehfeld- und Pendeltechnik (T3) zeigte gegenuber der Photonen/Elektronen-Technik und der einfachen Stehfeld/Pendel-Technik bei gleicher Auslastung in PTV und Boost zumindest eine bessere Schonung der kontralateralen Parotis. Dmean dieser Parotis lag bei T3 unterhalb der bisher von den Autoren angenommenen TD50 von 37 Gy (95%-Konfidenzintervall 32–43 Gy) und konnte folglich zu einer Schonung dieser Druse und damit zur Verringerung der Xerostomie beitragen.

Simultaneous radiochemotherapy (RCT) is the treatment of choice for locally advanced head and neck cancers. In order to evaluate the toxicity and the survival rates, we investigated the use of a very aggressive combination protocol that included cisplatinum and paclitaxel combined with hyperfractionated-accelerated radiotherapy. The final results of the phase II study are listed below.For the phase II trial 32 patients (29 male, 3 female) with histologically diagnosed locally advanced non-metastatic squamous cell carcinoma of the head and neck in stage III/IV were treated from 1999 to 2003. Radiotherapy was administered as hyperfractionated-accelerated to a total dose of 70.6 Gy. The chemotherapy regime included administering cisplatinum on d 1-5 and on d 29-33 at doses of 20 mg/m(2) and during the entire course of treatment paclitaxel was administered twice a week at doses of 25 mg/m(2).The 5-yr overall and disease-free survival rates were 48% and 43%. Twenty-two (69%) patients reached a clinically complete response and 8 (25%) a partial response (for two of the patients the response rate is not known). Two (6%) patients died during the treatment. Seven (22%) patients developed local recurrences and six of these patients have in the meantime died. With regards to the four (12%) patients who developed distant metastases, three of them have in the meantime died and two (6%) patients have died as a result of secondary malignancies. Seven out of 25 (28%) patients developed grade 3 erythema and 22 out of 31 (71%) patients developed grade 3 mucositis. No cases of grade 4 mucositis were observed; however, one patient out of 25 (4%) was classified with grade 4 dermatitis. One out of 24 (4%) patients developed grade 2 liver toxicity and 1 out of 22 patients (5%) developed grade 3 thrombopenia. Seven out of 25 patients (28%) developed a grade 3 leukopenia, and 2 out of 25 patients (8%) experienced a grade 4 eutropenic infection. Dysphagia was a significant late toxicity. Out of 24 patients, 4 (17%) developed a grade 3 dysphagia and 1 (4%) patient developed a grade 3 xerostomia. An osteoradionecrosis was seen in 2 out of 24 (8%) patients.This very aggressive radiochemotherapy protocol yielded excellent response and overall survival rates; however it is associated with a very high rate of acute toxicity. Therefore, in such cases where acute toxicity resulted, extensive supportive care is required.

Die Strahlentherapie bei Kopf-Hals-Tumoren fuhrt in aller Regel zu einer Schadigung der Speicheldrusen und somit auch zu einer dauerhaften Mundtrockenheit. Ziel dieser Untersuchung war es, eine moderne dreidimensionale Konformationsbestrahlungstechnik („three-dimensional conformal radiotherapy“ [3D-CRT]) fur Kopf-Hals-Tumoren zu etablieren, um im Vergleich zur konventionellen Bestrahlungstechnik (K-RT) mit Photonen und Elektronen Xerostomien zu vermeiden. Zwischen April 2002 und September 2003 wurden in einer prospektiven, nicht randomisierten Studie 32 Patienten (25 Manner, sieben Frauen, mittleres Alter: 58 Jahre) mit malignen Tumoren im Kopf-Hals-Bereich nach Operation oder bei Inoperabilitat mit einer kurativen Radiotherapie bzw. Radiochemotherapie behandelt. 10/32 Patienten (31%) erhielten die ubliche K-RT, die ubrigen 22/32 Patienten (69%) wurden mittels 3D-CRT (sechs bis acht Photonenstehfelder) behandelt. Als Mas fur die Strahlenbelastung der Parotiden wurde die mediane Parotisdosis in Gray (Dmean-Wert) als Mittelwert der Dmean-Dosen beider Parotiden aus den Dosis-Volumen-Histogrammen (DVH) anhand der CT-Schnitte bei der dreidimensionalen Planung bestimmt. Die Ermittlung der Dosis-Wirkungs-Kurven erfolgte mit Hilfe des logistischen Modells. Gemessen wurde der quantitative Faktor des Speichels als die stimulierte Speichelfliesrate (in ml/5 min) vor, zum Ende sowie 1, 6 und 12 Monate nach Abschluss der Behandlung. Im Trend war uber den gesamten Beobachtungszeitraum der Speichelfluss in der Gruppe mit 3D-CRT hoher als in der Gruppe mit K-RT (Zeitpunkt 10 Wochen nach Radiotherapiebeginn 3D-CRT vs. K-RT mit 1,56 ± 1,6 vs. 0,82 ± 1,2 ml/5 min; p < 0,1). Die mit K-RT behandelten Patienten hatten im Mittel signifikant hohere gemittelte Dmean-Werte als die mit 3D-CRT bestrahlten Patienten (p < 0,012). Patienten, die mit 3D-CRT wegen eines Larynx-/Hypopharynxkarzinoms behandelt wurden, hatten im Mittel signifikant niedrigere Dmean-Werte als Patienten, die wegen eines Mundhohlen-/Oropharynxkarzinoms mit 3D-CRT oder gleich welchen Tumorsitzes mit K-RT bestrahlt wurden (p < 0,003). Die nach NLSF-Methode berechnete 50%-Komplikationsrate der Speicheldrusen (TD50) lag bei 36,9 Gy (30,9–43,5 Gy; 95%-Vorhersageintervall). Der Anstieg k im Punkt TD50 wurde mit 7,7 (4,8–15,8; 95%-Vorhersageintervall) bestimmt. Die 3D-CRT eignet sich als Standard grundsatzlich fur Patienten mit Karzinomen im Mundhohlen-, Oro- und Hypopharynxbereich. Vor allem bei Patienten mit Larynx- und Hypopharynxkarzinomen konnen mittlere Dmean-Werte (ipsilaterale plus kontralaterale Glandula parotidea) erreicht werden, die nachweislich den Speichelfluss erhalten.

PURPOSE To determine prognostic factors in patients with cervical cancer treated with surgery followed by radiotherapy. PATIENTS AND METHODS In a retrospective analysis, patients treated at the Department of Radiotherapy, University of Halle-Wittenberg, Germany, from 1980 through 1993 were evaluated for local control, survival and treatment sequelae with special emphasis on prognostic factors. 298 patients (age 23-81 years, median 46 years) with cervical cancers were treated with surgery followed by radiotherapy to a minimum of 50 Gy. 250 patients received radiotherapy after radical hysterectomy with pelvic lymphadenectomy and 48 patients after hysterectomy. Most of the cancers were squamous cell carcinomas (81%) with few adenocarcinomas (12.4%). Grading was G1/G2 in 28.9% of the patients and G3/G4 in 39.6%. RESULTS The 5-year overall survival was 68.8% for the whole group, 70.5% for squamous cell carcinomas (n = 241), 64.4% for adenocarcinomas (n = 37; not significant), 80% for G1/G2 tumors (n = 86), and 69% for G3/G4 carcinomas (n = 118; p = 0.074). Survival dependent on tumor size and positive nodes was 76.2% (n = 94) for pT1N0, 65.8% for pT1N+ (n = 31), 68.2% for pT2N0 (n = 62), and 41.4% for pT2N+ (n = 35). An impact of grading on 5-year survival was only found in patients with positive nodes: G1/G2N0 84% (n = 62) versus G1/G2N+ 64.8% (n = 23); G3/G4N0 79.6% (n = 71) versus G3/G4N+ 39.9% (n = 31). The number of positive nodes was the strongest prognostic factor. Multivariate analysis (Cox regression) established a risk factor of 3.06 (p < 0.01) for positive nodes, of 1.7 for grading G1/G2 versus G3/G4 (p = 0.087), and of 1.3 for tumor size (pT1 vs. pT2; p = 0.079). There were no differences in the clinical outcome between patients in stage pT1 with or without lymphadenectomy (75% [n = 130] vs. 79% [n = 39]). CONCLUSION In patients with cervical cancers treated with surgery and radiotherapy, positive nodes were an independent prognostic factor for local control and survival and should be an indication for additional chemotherapy. A value of lymphadenectomy for survival in this group of irradiated patients could not be established.

Malignant diseases of the orbit are multifaceted and require in the majority of the cases an interdisciplinary treatment. Advances in radiotherapy, surgery and chemotherapy make a high cure rate possible, especially in children's tumors. In adults these tumors reach a tumor control rate of nearly 90 %, even with preservation of the eye in most of the cases. There are only two curative therapy options for tumors in this region: radiotherapy and surgery. The therapy for tumors of the eye and the orbit require the total spectrum of the radiotherapeutic techniques depending on the tumor entity, its spread and localization. In a prevailing number of malignant tumors (tumors of the eyelids, tear glands, orbit, metastases) the application of the radiotherapy as an external, fractionated radiotherapy is standard practice, if necessary in combination with operation and/or chemotherapy. Particularly in the therapy for ocular tumors brachytherapy with radionuclides (e. g., ruthenium) is possible and in a few centers world-wide proton therapy is available. As an alternative procedure in special modalities, stereotactic radiotherapy may be considered. Altogether the new radiotherapy techniques permit a dose increase in the tumor region and/or a reduction of the doses to healthy tissues and lead so to a better local tumor control rate and a decrease in acute and chronic side effects.