Chemoradiotherapy plus hyperthermia (CRTH) versus chemoradiotherapy (CRT) alone in neoadjuvant treatment of soft tissue sarcoma: tumor response, treatment toxicity and disease control.

INTRODUCTION: Neoadjuvant chemotherapy and radiotherapy for the management of soft tissue sarcomas (STS) are still preferably delivered sequentially, with or without concurrent hyperthermia. Concurrent delivery of chemo-, radio- and thermotherapy may produce synergistic effects and reduce chemotherapy-free intervals. The few available studies suggest that concurrent chemoradiation (CRT) has a greater local effect. Data on the efficacy and toxicity of adding hyperthermia to CRT (CRTH) are sparse. MATERIALS AND METHODS: A cohort of 101 patients with STS of the extremities and trunk who received CRT (n = 33) or CRTH (n = 68) before resection of macroscopic tumor (CRT: n = 19, CRTH: n = 49) or re-resection following a non-oncological resection, so called 'whoops procedure', (CRT: n = 14, CRTH: n = 19) were included in this retrospective study. CRT consisted of two cycles of doxorubicine (50 mg/m2 on d2) plus ifosfamide (1500 mg/m2 on d1-5, q28) plus radiation doses of up to 60 Gy. Hyperthermia was delivered in two sessions per week. RESULTS: All patients received the minimum dose of 50 Gy. Median doses of ifosfamide and doxorubicin were comparable between CRT (75%/95%) and CRTH (78%/97%). The median number of hyperthermia sessions was seven. There were no differences in acute toxicities. Major wound complications occurred in 15% (CRT) vs. 25% (CRTH) (p = 0.19). In patients with macroscopic disease, the addition of hyperthermia resulted in a tendency toward improved remission: regression ≥90% occurred in 21/48 (CRTH) vs. 4/18 (CRT) patients (p = 0.197). With a median postoperative follow-up of 72 months, 6-year local control and overall survival rates for CRTH vs. CRT alone were 85 vs. 78% (p = 0.938) and 79 vs. 71% (p = 0.215). CONCLUSIONS: Both CRT and CRTH are well tolerated with an expected rate of wound complications. The results suggest that adding hyperthermia may improve tumor response.

12â€¯× 6 Gy stereotactic radiotherapy for lung tumors. Is there a difference in response between lung metastases and primary bronchial carcinoma?

PURPOSE: The aim of this study was to evaluate the safety and long-term tumor control after stereotactic radiotherapy (SRT) with 12â€¯× 6 Gy of patients with primary bronchial carcinoma (BC) or with pulmonary metastases (MET) of various solid tumors. Local progression-free survival (LPFS), progression-free survival (PFS), overall survival (OS), and prognostic factors were compared. METHODS: Between May 2012 and January 2020, 168 patients with 206 pulmonary lesions (170 MET and 36 primary BC) were treated with 12â€¯× 6 Gy (BED10 116 Gy). The irradiated pulmonary MET were from the following cancers: 47 (27.6%) head and neck, 37 (21.8%) rectum or colon, 30 (17.6%) bronchial, 13 (7.6%) malignant melanoma, 9 (5.3%) esophageal, 9 (5.3%) sarcoma, and 25 (14.8%) other. RESULTS: The median follow-up was 16.26 months (range: 0.46-89.34) for BC and 19.18 months (0.89-91.11) for MET. Survival rates at 3 years were: OS 43% for BC and 35% for MET; LPFS BC 96% and MET 85%; PFS BC 35% and MET 29%. The most frequently observed grade 3 adverse events (AEs) were pneumonitis (5.9% BC, 4.8% MET), pulmonary fibrosis (2.9% BC, 4% MET), and pulmonary embolism (2.9% BC, 0.8% MET). The favorable prognostic effects on overall survival of patients with MET were female gender (log-rank: p < 0.001), no systemic progression (log-rank; p = 0.048, multivariate COX regression p = 0.039), and malignant melanoma histology (log-rank; p = 0.015, multivariate COX regression p = 0.020). For patients with BC, it was tumor location within the lower lobe (vs. upper lobe, log-rank p = 0.027). LPFS of patients with metastatic disease was beneficially influenced by female gender (log-rank: p = 0.049). CONCLUSION: The treatment concept of 12â€¯× 6 Gy is associated with 96% local progression-free survival for BC and 85% for pulmonary metastases after 3 years. There was no difference in response after SRT of primary lung carcinoma or pulmonary metastases.

Patterns of care analysis for salivary gland cancer: a survey within the German Society of Radiation Oncology (DEGRO) and recommendations for daily practice.

BACKGROUND: Salivary gland cancer (SGC) is rare and a heterogeneous type of cancer. Prospective randomized trials are lacking. No guideline focusing on standard procedures of radiotherapy (RT) in the treatment of SGC exists. Therefore, we surveyed the members of the German Society of Radiation Oncology (DEGRO) to gain information about current therapeutic strategies of SGC. METHODS: An anonymous questionnaire was designed and made available on the online platform umfrageonline.com. The corresponding link was sent to all DEGRO members who provided their user data for contact purposes. Alternatively, a PDF printout version was sent. Frequency distributions of responses for each question were calculated. The data were also analyzed by type of institution. RESULTS: Sixty-seven responses were received, including answers from 21 university departments, 22 non-university institutions, and 24 radiation oncology practices. Six participants reported that their departments (practice: n = 5, non-university hospital: n = 1) did not treat SGC, and therefore the questionnaire was not completed. Concerning radiation techniques, target volume definition, and concomitant chemotherapy, treatment strategies varied greatly among the participants. Comparing university vs. non-university institutions, university hospitals treat significantly more patients with SGC per year and initiated more molecular pathological diagnostics. CONCLUSION: SGC represents a major challenge for clinicians, as reflected by the inhomogeneous survey results regarding diagnostics, RT approaches, and systemic therapy. Future prospective, multicenter clinical trials are warranted to improve and homogenize treatment of SGC and to individualize treatment according to histologic subtypes and risk factors.

Radio(chemo)therapy in anaplastic thyroid cancer-high locoregional but low distant control rates-a monocentric analysis of a tertiary referral center.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a lethal disease with highly aggressive disease progression. This study analyses the influence of radio(chemo)therapy, R(C)T, on disease control, survival rates and predictors for survival. PATIENTS AND METHODS: A total of 33 patients with ATC, treated at a tertiary referral center between May 2001 and April 2020 were included. Univariate and multivariate analysis were used to investigate correlates of R(C)T and predictors on disease control and survival rates. RESULTS: Median follow-up was 4 months. In UICC stage IVA and IVB median overall survival (OS) was 8 months, median progression-free survival (PFS) was 6 months. Patients with UICC stage IVA and IVB and patients being irradiated with a radiation dose of more than 60 Gy showed increased OS. Of these patients, 3 were alive and free from disease. All of them receiving cisplatin-based radiochemotherapy and a minimum radiation dose of 66 Gy. UICC stage IVC showed a median OS of 2.5 months and a median PFS of 1 month. Only 2 of 16 patients had local failure. CONCLUSION: Depending on UICC stage, RT with high radiation dose can lead to improved OS or at least higher locoregional control. A limiting factor is the high incidence of distant metastases; therefore modern systemic treatment options should be integrated into multimodal therapy concepts.

Factors influencing downstaging after neoadjuvant long-course chemoradiotherapy in rectal carcinoma.

PURPOSE: This single-centre cohort study was designed to identify factors that can predict primary tumour downstaging by neoadjuvant chemoradiotherapy (nCRT) in rectal carcinoma. METHODS: Prospectively collected data from 555 patients with clinical T category (cT) cT3-4 rectal carcinoma treated between 1995 and 2019 were retrospectively analysed. All patients received long-term neoadjuvant chemoradiotherapy followed by surgery with curative intent at the Department of Surgery, University Hospital Erlangen, Germany. Patient-, tumour- and treatment-related factors with a potential impact on the downstaging of rectal carcinoma to pathological T category (pT) ≤ ypT2 and ypT0 were analysed in univariate and multivariate logistic regression analyses. The prognosis of patients with and without downstaging of the primary tumour was compared. RESULTS: A total of 288 (51.9%) patients showed downstaging to ≤ ypT2. Eighty-six (15.5%) patients achieved clinical complete regression (ypT0). In the multivariate logistic regression analysis, the factors cT category, BMI, ECOG score, CEA, histological type, extension in the rectum and year of the start of treatment were found to be independent factors for predicting downstaging to ≤ ypT2 after neoadjuvant chemoradiotherapy. The year of treatment initiation also remained an independent significant predictor for pathological complete regression. The prognosis was superior in patients with downstaging to ≤ ypT2 in terms of locoregional and distant recurrence as well as disease-free and overall survival. CONCLUSION: Factors predicting downstaging after long-term nCRT could be identified. This may be helpful for counselling patients and selecting the optimal treatment for patients with advanced rectal carcinoma.

High-grade salivary gland cancer: is surgery followed by radiotherapy an adequate treatment to reach tumor control? Results from a tertiary referral centre focussing on incidence and management of distant metastases.

PURPOSE: Salivary Gland cancer (SGC) is a rare and heterogenous group of tumors. Standard therapeutic options achieve high local but poor distant control rates, especially in high-grade SGC. The aim of this monocentric study was to evaluate patterns of recurrence and its treatment options (local ablative vs. systemic) in a homogenously treated patient population with high-grade SGC after surgery and radio(chemo)therapy. METHODS: Monocentric, retrospective study of patients with newly diagnosed high-grade salivary gland cancer. We retrospectively reviewed clinical reports from 69 patients with high-grade salivary gland cancer in a single-center audit. Survival rates were calculated using the Kaplan-Meier method and prognostic variables were analyzed (univariate analysis: log-rank test; multivariate analysis: Cox regression analysis). RESULTS: The median time of follow-up was 31 months. After 5 years, the cumulative overall survival was 65.2%, cumulative incidence of local recurrence was 7.2%, whereas the cumulative incidence of distant metastases was 43.5% after 5 years. 30 of 69 patients developed distant metastases during the time of follow-up, especially patients with adenoid cystic carcinoma, salivary duct carcinoma, adenocarcinoma NOS and acinic cell carcinoma with high-grade transformation. The most common type of therapy therefore was chemotherapy (50%). 85.7% of patients with local ablative therapy of distant metastases show disease progression during follow-up afterwards. CONCLUSION: With surgery and radio-chemotherapy, a high rate of loco-regional control is reached, but over 40% of patients develop distant metastases in the further follow-up which usually present a diffuse pattern involving in a diffuse metastases. Therefore, in the future, intensified interdisciplinary combination therapies even in the first-line treatment in certain subtypes of high-grade SGC should be investigated.

[Highlights from the 2021 ASCO and ESMO annual meetings on radiotherapy of head and neck cancer]. / Highlights der ASCO- und ESMO-Jahrestagungen 2021 zur Strahlentherapie von Kopf-Hals-Tumoren.

At this year's annual meetings of the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO), several studies on radiotherapy of locally advanced head and neck cancer were presented. For the indication of definitive radiochemotherapy, particularly the administration of immune checkpoint inhibitors concomitant to radiotherapy was investigated. In the phase III GORTEC-REACH trial, combined inhibition of epidermal growth factor receptor (EGFR) and programmed death-ligand (PD-L1) concomitant to radiotherapy of locally advanced head and neck cancer was inferior to platinum-based chemoradiotherapy. However, this therapeutic approach may be more efficient than radiotherapy with simultaneous EGFR inhibition alone. The concept of the phase II CheckRad-CD8 trial with induction chemoimmunotherapy followed by chemotherapy-free radioimmunotherapy after appropriate patient selection also proved to be highly efficient. In initial phase II trials, dose de-escalation of radiotherapy seems feasible for HPV-positive oropharyngeal cancer after appropriate patient selection both postoperatively (ECOG-ACRIN E3311 trial) and after induction therapy (Optima II trial). However, dose de-escalation should currently not be performed outside of clinical trials. In addition, first studies indicate a benefit of functional imaging (diffusion-weighted magnetic resonance imaging [MRI] or F­fluoromisonidazole positron-emission tomography [FMISO-PET]) to establish personalized dose concepts in radiotherapy.

Relevance of the time interval between surgery and adjuvant radio (chemo) therapy in HPV-negative and advanced head and neck carcinoma of unknown primary (CUP).

INTRODUCTION: In contrast to head and neck squamous cell carcinoma (HNSCC), the effect of treatment duration in HNSCC-CUP has not been thoroughly investigated. Thus, this study aimed to assess the impact of the time interval between surgery and adjuvant therapy on the oncologic outcome, in particular the 5-year overall survival rate (OS), in advanced stage, HPV-negative CUPs at a tertiary referral hospital. 5-year disease specific survival rate (DSS) and progression free survival rate (PFS) are defined as secondary objectives. MATERIAL AND METHODS: Between January 1st, 2007, and March 31st, 2020 a total of 131 patients with CUP were treated. Out of these, 59 patients with a confirmed negative p16 analysis were referred to a so-called CUP-panendoscopy with simultaneous unilateral neck dissection followed by adjuvant therapy. The cut-off between tumor removal and delivery of adjuvant therapy was set at the median, i.e. patients receiving adjuvant therapy below or above the median time interval. RESULTS: Depending on the median time interval of 55 days (d) (95% CI 51.42-84.52), 30 patients received adjuvant therapy within 55 d (mean 41.69 d, SD = 9.03) after surgery in contrast to 29 patients at least after 55 d (mean 73.21 d, SD = 19.16). All patients involved in the study were diagnosed in advanced tumor stages UICC III (n = 4; 6.8%), IVA (n = 27; 45.8%) and IVB (n = 28; 47.5%). Every patient was treated with curative neck dissection. Adjuvant chemo (immune) radiation was performed in 55 patients (93.2%), 4 patients (6.8%) underwent adjuvant radiation only. The mean follow-up time was 43.6 months (SD = 36.7 months). The 5-year OS rate for all patients involved was 71% (95% CI 0.55-0.86). For those patients receiving adjuvant therapy within 55 d (77, 95% CI 0.48-1.06) the OS rate was higher, yet not significantly different from those with delayed treatment (64, 95% CI 0.42-0.80; X2(1) = 1.16, p = 0.281). Regarding all patients, the 5-year DSS rate was 86% (95% CI 0.75-0.96). Patients submitted to adjuvant treatment in less than 55 d the DSS rate was 95% (95% CI 0.89-1.01) compared to patients submitted to adjuvant treatment equal or later than 55 d (76% (95% CI 0.57-0.95; X2(1) = 2.32, p = 0.128). The 5-year PFS rate of the entire cohort was 72% (95% CI 0.59-0.85). In the group < 55 d the PFS rate was 78% (95% CI 0.63-0.94) and thus not significantly different from 65% (95% CI 0.45-0.85) of the group ≥55 d; (X2(1) = 0.29, p = 0.589). CONCLUSIONS: The results presented suggest that the oncologic outcome of patients with advanced, HPV-negative CUP of the head and neck was not significantly affected by a prolonged period between surgery and adjuvant therapy. Nevertheless, oncologic outcome tends to be superior for early adjuvant therapy.

Questionnaire-based detection of immune-related adverse events in cancer patients treated with PD-1/PD-L1 immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICI) have become standard treatment in different tumor entities. However, safe treatment with ICI targeting the PD-1/PD-L1 axis requires early detection of immune-related adverse events (irAE). There exist different questionnaires of drug manufacturers for the detection of irAE that have not been validated so far. METHODS: The prospective non-interventional ST-ICI trial studied treatment with PD-1/PD-L1 ICI alone or combined with radiotherapy. In the current analysis, the detection rate of self-reported irAE with a patient questionnaire containing 41 different questions was compared to clinician-reported irAE. RESULTS: Between April 2017 and August 2019, a total of 104 patients were prospectively enrolled. NSCLC (44%) and HNSCC (42%) were the most frequent tumor entities. A total of 784 questionnaires were collected. A total of 29 irAE were reported by clinicians. The most frequent irAE was hypothyroidism (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), and pneumonitis (3%). Questions that became significantly more often positive at time points of clinician-reported irAE were "weight change", "difficulty to grip things", "bloody or mucous stool" and "insomnia". Self-reported organ-specific questions detected at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and skin irAE. It was not possible to detect hepatic irAE with the questionnaire. CONCLUSION: Questionnaires can help to detect gastrointestinal, lung, endocrine, or skin irAE, but not hepatic irAE. Questions on "weight change" and "insomnia" may help to increase the detection rate of irAE, besides organ-specific questions. These results are a valuable contribution to the future development of a specific and practicable questionnaire for early self-reported detection of irAE during ICI therapy in cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03453892 . Registered on 05 March 2018.

Magnetic resonance imaging for brain stereotactic radiotherapy : A review of requirements and pitfalls.

Due to its superior soft tissue contrast, magnetic resonance imaging (MRI) is essential for many radiotherapy treatment indications. This is especially true for treatment planning in intracranial tumors, where MRI has a long-standing history for target delineation in clinical practice. Despite its routine use, care has to be taken when selecting and acquiring MRI studies for the purpose of radiotherapy treatment planning. Requirements on MRI are particularly demanding for intracranial stereotactic radiotherapy, where accurate imaging has a critical role in treatment success. However, MR images acquired for routine radiological assessment are frequently unsuitable for high-precision stereotactic radiotherapy as the requirements for imaging are significantly different for radiotherapy planning and diagnostic radiology. To assure that optimal imaging is used for treatment planning, the radiation oncologist needs proper knowledge of the most important requirements concerning the use of MRI in brain stereotactic radiotherapy. In the present review, we summarize and discuss the most relevant issues when using MR images for target volume delineation in intracranial stereotactic radiotherapy.

Evidence for improved survival with bevacizumab treatment in recurrent high-grade gliomas: a retrospective study with ("pseudo-randomized") treatment allocation by the health insurance provider.

INTRODUCTION: Despite a large number of trials, the role of bevacizumab (BEV) in the treatment of recurrent high-grade gliomas is still controversial. Evidence regarding an effect on overall survival in this context is ultimately inconclusive. At the Department of Radiation Oncology at Erlangen, Germany we treated a large cohort of patients with recurrent gliomas where bevacizumab use was determined exclusively by the health care provider's approval of reimbursement. METHODS: 61 patients (between 06/2008 and 01/2014) with recurrent high-grade gliomas had reimbursement requests for BEV sent to their health insurance. 37 patients out of 61 (60.7%) had their requests approved and therefore received bevacizumab (BEV-arm) as part of their treatment. The remaining 24 (39.3%) patients received standard therapy without bevacizumab (non-BEV-arm). Survival endpoints were defined with reference to the first BEV request to the health insurance provider. RESULTS: Median overall survival (OS) for the whole cohort was 7.0 months. OS was significantly better for BEV vs. Non-BEV patients (median, 10.3 vs. 4.2 months, logrank p = 0.023). There was an increased BEV benefit in cases of higher-order recurrences (first order recurrence BEV vs. Non-BEV, 12.5 vs. 10.2 months, p = 0.578) (second or higher order of recurrence, 9.9 vs. 2.6 months, p = 0.010). On multivariate analysis for overall survival the prognostic impact of bevacizumab (HR = 0.43, p = 0.034) remained significant. CONCLUSION: Our results suggest an influence of BEV on overall survival in a heavily pretreated patient population suffering from high-grade gliomas with BEV benefit being greatest in case of second or later recurrence.

The influence of postoperative complications on long-term prognosis in patients with colorectal carcinoma.

BACKGROUND: The impact of postoperative complications (POCs) on the long-term prognosis of patients with colorectal carcinoma was analysed with respect to their severity according to the Clavien-Dindo classification (CDC). METHODS: The prospectively collected data of 2158 patients who underwent curative resection of a colorectal carcinoma (1168 rectal carcinomas, 990 colon carcinomas) without distant metastases from 1995 to 2014 were analysed. The POCs were documented in a standardized form and graded with the CDC. Patients who died postoperatively (CDC grade V, 1.7%) were excluded. RESULTS: In total, 467 patients (21.6%) had POCs: CDC I, 141 (6.5%); CDC II, 162 (7.5%); CDC III, 112 (5.2%); and CDC IV, 52 (2.4%). More POCs and higher CDC grades were found in men, ASA III-IV patients, rectal carcinoma patients, and patients who underwent abdominoperineal excisions or multivisceral resections. The 5-year locoregional recurrence rate was 5.3% in patients without POCs and 6.6% in patients with POCs. It was highest in CDC III patients (12.9%), which was confirmed in multivariate analysis (HR 2.2; p = 0.005). The 5-year distant metastasis rate was 15.9% in CDC 0 patients and 19.5% in CDC I-IV patients. In multivariate analysis, distant metastasis was highest in CDC III patients (HR 1.7; p = 0.020). The 5-year overall survival rate was 83.5% in patients without POCs and 73.5% in patients with POCs. It was worst in CDC IV patients (63.1%), which was confirmed by multivariate analysis (HR 1.9; p = 0.001). CONCLUSION: Patients with POCs after colorectal surgery have a poor long-term prognosis. As the CDC grade increases, survival deteriorates.

Single-cycle induction chemotherapy before chemoradiotherapy or surgery in functionally inoperable head and neck squamous cell carcinoma: 10-year results.

INTRODUCTION: The response to induction chemotherapy (IC) predicts local control after conservative treatment of laryngeal, meso- and hypopharyngeal head and neck squamous cell carcinoma (HNSCC) and can thus help to avoid surgery. Single-cycle induction chemotherapy may help to maintain a low local recurrence rate while keeping the overall toxicity manageable. However, long-term data on single-cycle IC response by tumor location is lacking. METHODS: N = 102 patients with functionally inoperable primary HNSCC of the larynx (n = 43), hypopharynx (n = 42) or mesopharynx/tongue (n = 17) received one cycle of docetaxel (75 mg/m2, d1) plus cisplatin (30 mg/m2, d1-3) or carboplatin (AUC 1.5, d1-3) and a response evaluation 3 weeks later. Responders (≥ 30% tumor size reduction and ≥ 20% SUVmax decrease in 18F-FDG PET/CT) were recommended chemoradiotherapy (CRT), and non-responders surgery. RESULTS: The overall response rate was 72.5%. All 74 responders and 10 non-responders received primary CRT, and 18 patients received primary surgery after single-cycle IC. Overall 10-year local recurrence-free survival (LRFS) was 73.7%. Three-year LRFS was 88.2% (mesopharynx/tongue), 88.2% (larynx), and 73.3% (hypopharynx); p = 0.17. 3-year distant metastasis-free survival (DMFS) was 94.1% (mesopharynx/tongue), 88.0% (larynx) and 76.4% (hypopharynx); p > 0.05. This influenced the 3-year cancer-specific survival (CSS) for larynx (91.2%) vs. hypopharynx tumors (60.8%); p = 0.003, but CSS was not different to tumors in the mesopharynx/tongue (81.4%); p > 0.05. CONCLUSIONS: A single-cycle induction chemotherapy for HNSCC enables surgery plus adjuvant therapy as well as chemoradiotherapy. The long-term local and distant disease control was good but varied between tumors in the larynx and mesopharynx/tongue vs. hypopharynx.

Is there a patient population with squamous cell carcinoma of the head and neck region who might benefit from de-intensification of postoperative radiotherapy? : A monocentric retrospective analysis of a previously defined low-risk patient population treated with standard-of-care radiotherapy.

PURPOSE: The aim of this retrospective study was to evaluate the clinical outcome of a previously defined low-risk patient population with completely resected (R0) squamous cell carcinoma of the oral cavity, oropharynx, larynx (pT1-3, pN0-pN2b), hypopharynx (pT1-2, pN0-pN1), and the indication for postoperative radio(chemo)therapy. PATIENTS AND METHODS: According to predefined criteria, 99 patients with head and neck squamous cell carcinoma (SCC) who were treated at our institution from January 1, 2005 to December 31, 2014, were available for analysis. The Kaplan-Meier method was used for calculating survival and incidence rates. For univariate comparative analysis, the log-rank test was used for analyzing prognostic clinicopathologic parameters. RESULTS: Median follow-up was 67 months. Cumulative overall (OS) and disease-free survival (DFS) were 97.9%/94.7%/88.0% and 96.9%/92.6%/84.7% after 1, 2, and 5 years, respectively. Cumulative incidence of loco-regional recurrence (LRR), distant metastases (DM), and second cancer (SC) were 1.0%/1.0%/4.9%, 0.0%/3.4%/5.8%, and 2.1%/4.2%/13.1%, respectively. In univariate comparative analysis, location of the primary tumor in the oropharynx was a significant predictor for increased OS (p = 0.043) and DFS (p = 0.048). CONCLUSION: Considering the low disease relapse rates and high rates of therapy-induced late side effects, as well as the increased risk of developing SC, a prospective multicentric trial investigating de-escalation of radiotherapy in this clearly defined low-risk patient population was started and is still recruiting patients (DIREKHT-Trial, NCT02528955).

Time course of pain response and toxicity after whole-nerve-encompassing LINAC-based stereotactic radiosurgery for trigeminal neuralgia-a prospective observational study.

PURPOSE: To prospectively evaluate the time course of pain response and toxicity after linear accelerator-based whole-nerve-encompassing radiosurgery (LINAC-SRS) using a uniform treatment schedule for dosing and target volume definition in patients with refractory trigeminal neuralgia. METHODS: From December 2012 to December 2016, 21 patients were treated using a standardized protocol. Patients received LINAC-SRS with 70 Gy to the cisternal portion while aiming for the 90% isodose to fully envelope the nerve in one cross-sectional plane. Data on pain, analgesics, and toxicity were gathered prospectively. Four time intervals (1-6, 6-12, 12-18, and 18-24 months) were defined and compared to baseline and each other. RESULTS: The median follow-up from radiotherapy was 16 months. Freedom from pain was achieved at least once in 90.5, 81.0, and 85.7% of patients for everyday pain, rest pain, and pain peaks, respectively. At 1-6 months, pain was significantly reduced in everyday routine (mean VAS, 2.0/10 vs. 5.8/10; P = 0.004), at rest (1.5/10 vs. 4.0/10; P = 0.002), and for pain peaks (2.9/10 vs. 10/10; P < 0.001), as was the number of analgesics (mean 1.5 vs. 2.9; P < 0.001). No significant increase in pain or analgesics was observed for subsequent time intervals. At last follow-up, reduction in pain compared to baseline for everyday routine (2.1/10 vs. 5.8/10; P = 0.010) and for pain peaks (3.3/10 vs. 10/10; P < 0.001) was significant, whereas it was not for rest pain (1.8/10 vs. 3.9/10; P = 0.073). Most toxicities were related to trigeminal nerve impairment, with 42.9% reporting new-onset hypoesthesia at last follow-up. CONCLUSION: This study provides prospective data after whole nerve encompassing LINAC-SRS for trigeminal neuralgia. No significant pain relapse was observed.

Chemoradiotherapy with and without deep regional hyperthermia for squamous cell carcinoma of the anus.

PURPOSE: To compare results after chemoradiotherapy with and without deep regional hyperthermia in patients with anal cancer. METHODS: Between 2000 and 2015, a total of 112 consecutive patients with UICC stage I-IV anal cancer received chemoradiotherapy with 5­fluororuracil and mitomycin C (CRT). In case of insufficient tumor response 4-6 weeks after chemoradiotherapy, patients received an interstitial pulsed-dose-rate brachytherapy boost. Additionally, 50/112 patients received hyperthermia treatments (HCRT). RESULTS: Median follow-up was 41 (2-165) months. After 5 years follow-up, overall (95.8 vs. 74.5%, P = 0.045), disease-free (89.1 vs. 70.4%, P = 0.027), local recurrence-free (97.7 vs. 78.7%, P = 0.006), and colostomy-free survival rates (87.7 vs. 69.0%, P = 0.016) were better for the HCRT group. Disease-specific, regional failure-free, and distant metastasis-free survival rates showed no significant differences. The adjusted hazard ratios for death were 0.25 (95% CI, 0.07 to 0.92; P = 0.036) and for local recurrence 0.14 (95% CI, 0.02 to 1.09; P = 0.06), respectively. Grades 3-4 early toxicities were comparable with the exception of hematotoxicity, which was higher in the HCRT group (66 vs. 43%, P = 0.032). Incidences of late side effects were similar with the exception of a higher telangiectasia rate in the HCRT group (38.0 vs. 16.1%, P = 0.009). CONCLUSION: Additional regional hyperthermia improved overall survival, local control, and colostomy rates. Its potential beneficial role has to be confirmed in a prospective randomized setting. Therefore, the HyCAN trial has already been established by our group and is currently recruiting patients (Clinicaltrials.gov identifier: NCT02369939).

Patient's quality of life after surgery and radiotherapy for extremity soft tissue sarcoma - a retrospective single-center study over ten years.

BACKGROUND AND OBJECTIVES: The purpose of this study is to analyze major complication rates and different aspects of health-related quality of life (HRQoL) in extremity soft tissue sarcoma (STS) patients treated with or without radio (chemo) therapy and surgery. METHODS: We performed a retrospective analysis of all patients who underwent Extremity STS excision from 2004 to 2014 (182 patients included). Patients' data were collected from patients' records. HRQoL was assessed by using EORTC QLQ-C30. RESULTS: A total of 182 patients underwent sarcoma resection. After neoadjuvant radiochemotherapy (RCT), the major-complication rate amounted to 28% (vs. 7%, no radiotherapy, p <  0.001). Major-complication rates after adjuvant radiotherapy (RT) occurred in 8% (vs. 7%, no radiotherapy, p = 0.265). Comparison QoL scores between treating with neoadjuvant RCT or without RT revealed significant worse scores with neoadjuvant RCT. Further stratification of disease control of these patients showed significant reduced scores in the group of disease-free patients with neoadjuvant RCT compared to irradiated disease-free patients. DISCUSSION: To date, there have only been a few investigations of QoL in STS. Retrospective study on quality of life have limitations, like a lack of baseline evaluation of QoL. Patient candidated to radiation therapy could have had worse QoL baseline due to more advanced disease. Disease status of the patients who answered the questionnaires could have been an influence of QoL and we could show reduced scores in the group of disease-free patients with neoadjuvant RCT, but not for the patients with recurrence or metastasis, so it is very hard to discriminate whether radiation therapy could really have an impact or not. CONCLUSION: This study might assist in further improving the understanding of QoL in STS patients and may animate for prospective studies examining the oncological therapies impact on HRQoL.

The influence of tumour site on prognosis in metastatic colorectal carcinomas with primary tumour resection.

PURPOSE: The aim of our study was to compare the characteristics and prognosis between right- and left-sided metastatic colorectal carcinomas. METHODS: Data from 937 patients with stage IV colorectal carcinomas (synchronous distant metastasis) who had a resection of the primary tumour between 1985 and 2014 were analysed. Carcinomas in the caecum to transverse colon were defined as right-sided (n = 250; 26.7%). They were compared to tumours located from the splenic flexure to the rectum categorised as left-sided (n = 687; 73.3%). RESULTS: In right-sided carcinomas, we observed significantly more female patients (50.8 vs 36.2%; p < 0.001), more unfavourable histological types (24.0 vs 8.6%; p < 0.001), more M1c carcinomas (metastases to the peritoneum ± others; 32.0 vs 14.4%; p < 0.001) and more emergencies (11.6 vs 7.1%; p = 0.029), while multimodal treatment was utilised in fewer patients (51.6 vs 63.8%; p = 0.001) and curative resections were less frequently (24.1 vs 35.4%; p = 0.002). Prognosis was significantly worse in patients with right-sided carcinomas (2-year-survival 27.2 vs 44.6%, p < 0.01). This difference was more pronounced after R2 resection (15.3 vs 29.7%; p < 0.001), than after macroscopic curative resection (2-year-survival 63.9 vs 71.9%; p = 0.106). In multivariate Cox regression analysis, tumour site was found to be an independent prognostic factor for overall survival (HR 1.2; 95% CI 1.0-1.5; p = 0.012). During the three 10-year periods, the prognosis improved equally in patients with right- and left-sided carcinomas, while the differences in survival remained identical. CONCLUSIONS: In a surgical patient cohort undergoing primary tumour resection, significant differences in prognosis were observed between patients with metastatic right- and left-sided colorectal carcinomas.

Repeating of local therapy of distant metastases increases overall survival in patients with synchronous metastasized rectal cancer-a monocentric analysis.

PURPOSE: The aim was to evaluate the outcome of treatment-naive patients with synchronous metastatic rectal cancer after chemotherapy with FOLFOXIRI followed by local therapeutic procedures of all tumor lesions as complete as possible. METHODS: We reviewed data of 30 patients with synchronous distant metastatic rectal cancer who underwent chemotherapy with FOLFOXIRI and subsequent local therapy in our institution. RESULTS: Median follow-up was 28 months (range: 8; 74). Cumulative overall survival (OS) and progression-free survival (PFS) was 93.3, 76.9, 55.6% and 46.2, 29.7, 29.7% after 1, 2, 4 years. Non-response to chemotherapy with FOLFOXIRI was associated with a highly significant decreased OS (p < 0.0001). The consistent use of local ablative procedures led to a statistically significant increase in OS (p < 0.0001), but not in PFS (p = 0.635). Patients with ≤ 4 distant metastases showed a better OS (p = 0.033). CONCLUSIONS: Response to intensified first-line chemotherapy with FOLFOXIRI, treatment of the primary rectal tumor, and repeated thorough local ablative procedures in patients with synchronous metastasized rectal cancer may lead to long-term survival, even in a subset of patients with unresectable disease at initial diagnosis.