A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation.

PURPOSE: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiation therapy is considered the standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older patients with HNSCC. METHODS AND MATERIALS: The SENIOR study is an international multicenter cohort study including older patients (≥65 years) with HNSCC treated with definitive radiation therapy at 13 academic centers in the United States and Europe. Patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) via Kaplan-Meier analyses. Fine-Gray competing risk regressions were performed regarding the incidence of locoregional failures and distant metastases. RESULTS: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n = 310; 44%), followed by cisplatin plus 5-fluorouracil (n = 137; 20%), carboplatin (n = 73; 10%), and mitomycin C plus 5-fluorouracil (n = 64; 9%). Carboplatin-based regimens were associated with diminished PFS (hazard ratio [HR], 1.39 [1.03-1.89]; P < .05) and a higher incidence of locoregional failures (subdistribution HR, 1.54 [1.00-2.38]; P = .05) compared with single-agent cisplatin, whereas OS (HR, 1.15 [0.80-1.65]; P = .46) was comparable. There were no oncological differences between single-agent and multiagent cisplatin regimens (all P > .05). The median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR, 0.71 [0.53-0.95]; P = .02), increased PFS (HR, 0.66 [0.51-0.87]; P = .003), and lower incidence of locoregional failures (subdistribution HR, 0.50 [0.31-0.80]; P = .004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR, 0.996 [0.993-0.999]; P = .009). CONCLUSIONS: Single-agent cisplatin can be considered in the standard chemotherapy regimen for older patients with HNSCC who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant in older patients with HNSCC.

Benchmarking ChatGPT-4 on a radiation oncology in-training exam and Red Journal Gray Zone cases: potentials and challenges for ai-assisted medical education and decision making in radiation oncology.

Purpose: The potential of large language models in medicine for education and decision-making purposes has been demonstrated as they have achieved decent scores on medical exams such as the United States Medical Licensing Exam (USMLE) and the MedQA exam. This work aims to evaluate the performance of ChatGPT-4 in the specialized field of radiation oncology. Methods: The 38th American College of Radiology (ACR) radiation oncology in-training (TXIT) exam and the 2022 Red Journal Gray Zone cases are used to benchmark the performance of ChatGPT-4. The TXIT exam contains 300 questions covering various topics of radiation oncology. The 2022 Gray Zone collection contains 15 complex clinical cases. Results: For the TXIT exam, ChatGPT-3.5 and ChatGPT-4 have achieved the scores of 62.05% and 78.77%, respectively, highlighting the advantage of the latest ChatGPT-4 model. Based on the TXIT exam, ChatGPT-4's strong and weak areas in radiation oncology are identified to some extent. Specifically, ChatGPT-4 demonstrates better knowledge of statistics, CNS & eye, pediatrics, biology, and physics than knowledge of bone & soft tissue and gynecology, as per the ACR knowledge domain. Regarding clinical care paths, ChatGPT-4 performs better in diagnosis, prognosis, and toxicity than brachytherapy and dosimetry. It lacks proficiency in in-depth details of clinical trials. For the Gray Zone cases, ChatGPT-4 is able to suggest a personalized treatment approach to each case with high correctness and comprehensiveness. Importantly, it provides novel treatment aspects for many cases, which are not suggested by any human experts. Conclusion: Both evaluations demonstrate the potential of ChatGPT-4 in medical education for the general public and cancer patients, as well as the potential to aid clinical decision-making, while acknowledging its limitations in certain domains. Owing to the risk of hallucinations, it is essential to verify the content generated by models such as ChatGPT for accuracy.

Positive factors on survival of head and neck cancer of unknown primary: what the clinician can do.

BACKGROUND: Management of patients with head and neck cancer of unknown primary (HNCUP) is challenging. AIMS/OBJECTIVES: To provide a long-term analysis focusing on protective survival factors for clinical decision-making. Furthermore, the prognostic value of the current N classification system was evaluated. MATERIAL AND METHODS: We retrospectively analyzed patients with HNCUP between 2003 and 2016. Univariate and multivariate analyses were used to investigate predictors of overall survival (OS). RESULTS: A primary tumor was found in 67 of 290 patients with suspected HNCUP, leaving after exclusion 141 HNCUP cases for analysis, who received multi-step therapy (MST) (n = 108) or single therapy (n = 28). Chemotherapy (CT) (n = 101), curative MST, ≤3 positive lymph nodes (LN) (n = 33), squamous cell carcinoma (SCC) (n = 123), HPV+ (n = 21), M0 (n = 70) increased OS by 21.8%, 24.4%, 12.7%, 6.8%, 18.7%, 29.6%, respectively. 5- and 10-year OS was 78.1%/66.6%. The number of metastatic LNs predicted OS is better than N classification. CONCLUSION AND SIGNIFICANCE: Aspects for clinical decision-making: Curative MST and SCC histology were the most significant predictors for improved OS. Categorizing LN into 1, 2-3, and >3 LNs was more significant than the traditional N classification. The addition of CT to curative MST has a stronger impact on survival than HPV and N classifications.

Clinical application of breathing-adapted 4D CT: image quality comparison to conventional 4D CT.

PURPOSE: 4D CT imaging is an integral part of 4D radiotherapy workflows. However, 4D CT data often contain motion artifacts that mitigate treatment planning. Recently, breathing-adapted 4D CT (i4DCT) was introduced into clinical practice, promising artifact reduction in in-silico and phantom studies. Here, we present an image quality comparison study, pooling clinical patient data from two centers: a new i4DCT and a conventional spiral 4D CT patient cohort. METHODS: The i4DCT cohort comprises 129 and the conventional spiral 4D CT cohort 417 4D CT data sets of lung and liver tumor patients. All data were acquired for treatment planning. The study consists of three parts: illustration of image quality in selected patients of the two cohorts with similar breathing patterns; an image quality expert rater study; and automated analysis of the artifact frequency. RESULTS: Image data of the patients with similar breathing patterns underline artifact reduction by i4DCT compared to conventional spiral 4D CT. Based on a subgroup of 50 patients with irregular breathing patterns, the rater study reveals a fraction of almost artifact-free scans of 89% for i4DCT and only 25% for conventional 4D CT; the quantitative analysis indicated a reduction of artifact frequency by 31% for i4DCT. CONCLUSION: The results demonstrate 4D CT image quality improvement for patients with irregular breathing patterns by breathing-adapted 4D CT in this first corresponding clinical data image quality comparison study.

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy.

Importance: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and these patients are underrepresented in clinical trials. It is unclear whether the addition of chemotherapy or cetuximab to radiotherapy is associated with improved survival in older adults with HNSCC. Objective: To examine whether the addition of chemotherapy or cetuximab to definitive radiotherapy is associated with improved survival in patients with locoregionally advanced (LA) HNSCC. Design, Setting, and Participants: The Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy (SENIOR) study is an international, multicenter cohort study including older adults (≥65 years) with LA-HNSCCs of the oral cavity, oropharynx/hypopharynx, or larynx treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between January 2005 and December 2019 at 12 academic centers in the US and Europe. Data analysis was conducted from June 4 to August 10, 2022. Interventions: All patients underwent definitive radiotherapy alone or with concomitant systemic treatment. Main Outcomes and Measures: The primary outcome was overall survival. Secondary outcomes included progression-free survival and locoregional failure rate. Results: Among the 1044 patients (734 men [70.3%]; median [IQR] age, 73 [69-78] years) included in this study, 234 patients (22.4%) were treated with radiotherapy alone and 810 patients (77.6%) received concomitant systemic treatment with chemotherapy (677 [64.8%]) or cetuximab (133 [12.7%]). Using inverse probability weighting to attribute for selection bias, chemoradiation was associated with longer overall survival than radiotherapy alone (hazard ratio [HR], 0.61; 95% CI, 0.48-0.77; P < .001), whereas cetuximab-based bioradiotherapy was not (HR, 0.94; 95% CI, 0.70-1.27; P = .70). Progression-free survival was also longer after the addition of chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P < .001), while the locoregional failure rate was not significantly different (subhazard ratio, 0.62; 95% CI, 0.30-1.26; P = .19). The survival benefit of the chemoradiation group was present in patients up to age 80 years (65-69 years: HR, 0.52; 95% CI, 0.33-0.82; 70-79 years: HR, 0.60; 95% CI, 0.43-0.85), but was absent in patients aged 80 years or older (HR, 0.89; 95% CI, 0.56-1.41). Conclusions and Relevance: In this cohort study of older adults with LA- HNSCC, chemoradiation, but not cetuximab-based bioradiotherapy, was associated with longer survival compared with radiotherapy alone.

Low-dose radiotherapy of osteoarthritis: from biological findings to clinical effects-challenges for future studies.

Osteoarthritis (OA) is one of the most common and socioeconomically relevant diseases, with rising incidence and prevalence especially with regard to an ageing population in the Western world. Over the decades, the scientific perception of OA has shifted from a simple degeneration of cartilage and bone to a multifactorial disease involving various cell types and immunomodulatory factors. Despite a wide range of conventional treatment modalities available, a significant proportion of patients remain treatment refractory. Low-dose radiotherapy (LDRT) has been used for decades in the treatment of patients with inflammatory and/or degenerative diseases and has proven a viable option even in cohorts of patients with a rather poor prognosis. While its justification mainly derives from a vast body of empirical evidence, prospective randomized trials have until now failed to prove the effectiveness of LDRT. Nevertheless, over the decades, adaptions of LDRT treatment modalities have evolved using lower dosages with establishment of different treatment schedules for which definitive clinical proof is still pending. Preclinical research has revealed that the immune system is modulated by LDRT and very recently osteoimmunological mechanisms have been described. Future studies and investigations further elucidating the underlying mechanisms are an essential key to clarify the optimal patient stratification and treatment procedure, considering the patients' inflammatory status, age, and sex. The present review aims not only to present clinical and preclinical knowledge about the mechanistic and beneficial effects of LDRT, but also to emphasize topics that will need to be addressed in future studies. Further, a concise overview of the current status of the underlying radiobiological knowledge of LDRT for clinicians is given, while seeking to stimulate further translational research.

Differences and Similarities in the Pattern of Early Metabolic and Morphologic Response after Induction Chemo-Immunotherapy versus Induction Chemotherapy Alone in Locally Advanced Squamous Cell Head and Neck Cancer.

Background: In head and neck cancer patients, parameters of metabolic and morphologic response of the tumor to single-cycle induction chemotherapy (IC) with docetaxel, cis- or carboplatin are used to decide the further course of treatment. This study investigated the effect of adding a double immune checkpoint blockade (DICB) of tremelimumab and durvalumab to IC on imaging parameters and their significance with regard to tumor cell remission. Methods: Response variables of 53 patients treated with IC+DICB (ICIT) were compared with those of 104 who received IC alone. Three weeks after one cycle, pathologic and, in some cases, clinical and endoscopic primary tumor responses were evaluated and correlated with a change in 18F-FDG PET and CT/MRI-based maximum-standardized uptake values (SUVmax) before (SUVmaxpre), after treatment (SUVmaxpost) and residually (resSUVmax in % of SUVmaxpre), and in maximum tumor diameter (Dmax) before (Dmaxpre) and after treatment (Dmaxpost) and residually (resD). Results: Reduction of SUVmax and Dmax occurred in both groups; values were SUVmaxpre: 14.4, SUVmaxpost: 6.6, Dmaxpre: 30 mm and Dmaxpost: 23 mm for ICIT versus SUVmaxpre: 16.5, SUVmaxpost: 6.4, Dmaxpre: 21 mm, and Dmaxpost: 16 mm for IC alone (all p < 0.05). ResSUVmax was the best predictor of complete response (IC: AUC: 0.77; ICIT: AUC: 0.76). Metabolic responders with resSUVmax ≤ 40% tended to have a higher rate of CR to ICIT (88%; n = 15/17) than to IC (65%; n = 30/46; p = 0.11). Of the metabolic nonresponders (resSUVmax > 80%), 33% (n = 5/15) achieved a clinical CR to ICIT versus 6% (n = 1/15) to IC (p = 0.01). Conclusions: ICIT and IC quickly induce a response and 18F-FDG PET is the more accurate modality for identifying complete remission. The rate of discrepant response, i.e., pCR with metabolic nonresponse after ICIT was >30%.

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.

Extramedullary plasmacytoma: Tumor occurrence and therapeutic concepts-A follow-up.

BACKGROUND: Extramedullary plasmacytoma (EMP) is a solitary tumor consisting of neoplastic plasma cells, with very little to no bone marrow involvement. EMPs are usually located in the head and neck region, but can also occur along the digestive tract, in lungs, or extremities. METHODS: Following our publication on EMP, which appeared in 1999 (Cancer 85:2305-14), we conducted a literature search for EMP-related reports published between 1999 and 2021. The documented cases, as well as 14 of our own patients from the ENT Clinic Erlangen, were extensively analyzed. RESULTS: Between 1998 and 2021, 1134 patients with EMP were reported, for whom information about the tumor localization was available. Among those, 62.4% had EMP in the head and neck area and 37.6% in other body regions. Data on therapy were reported in 897 patients, including 34.3% who received radiation, 28.1% surgery, 22.6% a combination of surgery and radiation, and 15.9% another therapy. In 76.9% patients no recurrence or transformation to multiple myeloma (MM) was reported, 12.8% showed local recurrence and 10.2% developed MM. Radiotherapy alone was associated with a tendency for increased occurrence of MM. In patients with EMP of head and neck area, combination therapy (surgery and radiation) resulted in a 5-year overall survival rate of 98.3%, surgery alone of 92.4%, and radiotherapy of 92.7%. CONCLUSIONS: Collectively, our analyses indicate that surgical resection alone can achieve long-term tumor control in patients with EMP, if the tumor can be removed within safe limits without causing serious functional impairment. However, if this is not certain, either radiation or a combination of surgery and radiation therapy is suggested as an effective means of local tumor control.

Targeted Therapy, Chemotherapy, Immunotherapy and Novel Treatment Options for Different Subtypes of Salivary Gland Cancer.

Surgical resection remains the first line treatment for salivary gland cancer (SGC). In the case of locally advanced disease, surgery is followed by adjuvant radiotherapy. Surgical resection should be favored in resectable locoregional recurrent disease as well, and even the complete resection of all distant oligometastases has clinical benefit for the patients. For inoperable and disseminated metastatic disease, a multitude of systemic therapies including chemotherapy, targeted therapy, and immunotherapy are available. In this review, the current therapeutic options for inoperable recurrent or metastatic SGCs are summarized. Systemic treatment can achieve prolonged progression-free and overall survival, while the overall prognosis remains poor. Current clinical trials include only a limited number of patients and mostly combine different histologic subtypes. Additionally, no randomized controlled trial comparing different therapeutic options has been performed. In the future, further studies with a larger patient cohort and ideally only one histologic subtype are needed in order to improve the outcome for SGC patients. However, this may be difficult to accomplish due to the rarity and diversity of the disease. Additionally, molecular analyses need to be performed routinely in order to individualize treatment and to go one step further towards precision medicine.

The Prognostic Value of FoxP3+ Tumour-Infiltrating Lymphocytes in Rectal Cancer Depends on Immune Phenotypes Defined by CD8+ Cytotoxic T Cell Density.

Tumour-infiltrating FoxP3+ regulatory T cells have been identified as both positive and negative prognostic factors in colorectal cancer (CRC) and rectal cancer (RC). In this study we investigated whether immune phenotypes, defined by CD8+ cytotoxic T cell density, may influence the prognostic association of FoxP3+ T cell densities in RC. Tissue microarrays from 154 rectal cancer resections were immunohistochemically double stained for CD8 and FoxP3. CD8+ and FoxP3+ cell densities were measured in the stromal and intraepithelial compartment. Stromal FoxP3+ cell densities were not associated with 10-year overall survival (OS). In the "immune-desert" phenotype, defined by very low stromal CD8+ cell density, a high density of stromal FoxP3+ T cells displayed a tendency towards an association with decreased 10-year OS (p = 0.179). In "inflamed" tumours, defined by high intraepithelial CD8+ T cell infiltration, the opposite was the case and high stromal FoxP3+ T cell densities were a positive prognostic factor (p = 0.048). Additionally, patients with an increased FoxP3/CD8 cell density ratio demonstrated a strong trend towards decreased 10-year OS (p = 0.066). These contrasting findings suggest functional heterogeneity within the group of FoxP3+ T cells. They are consistent with experimental studies which reported suppressive and non-suppressive populations of FoxP3+ T cells in CRC. Furthermore, our study demonstrates that CD8 immunohistochemistry may act as an instrument to identify tumours infiltrated by possibly functionally differing FoxP3+ T cell subtypes.

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.

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.

Reduction of Elective Radiotherapy Treatment Volume in Definitive Treatment of Locally Advanced Head and Neck Cancer-Comparison of a Prospective Trial with a Revised Simulated Contouring Approach.

Definitive radiochemotherapy of locally advanced head and neck squamous cell cancer (HNSCC) achieves high locoregional tumor control rates; but is frequently associated with long-term toxicity. A future direction could be a de-escalation strategy focusing on treated volume rather than radiotherapy dose. This analysis evaluates radiotherapy dose and volume parameters of patients treated with a standard contouring approach in a clinical trial context compared with a revised volume-reduced contouring approach. In this case, 30 consecutive patients from the CheckRad-CD8 trial treated at a single study center were included in this analysis. Treatment toxicity and quality of life were assessed at the end of radiotherapy. Standard treatment plans (ST) following state of the art contouring guidelines that were used for patient treatment and volume reduced treatment plans (VRT) according to a revised simulated approach were calculated for each patient. Planning target volumes (PTV) and mean doses to 38 organs-at-risk structures were compared. At the end of radiotherapy patients reported high rates of mucositis; dysphagia and xerostomia. In addition; patient reported quality of life as assessed by the EORTC QLQ-HN35 questionnaire deteriorated. Comparing the two contouring approaches; the elective PTV_56 Gy and the high risk PTV_63 Gy (shrinking field) were significantly smaller in the VRT group. Significant reduction of mean dose to structures of the oral cavity; the larynx as well as part of the swallowing muscles and the submandibular glands was achieved in the simulated VRT-plan. Treatment de-intensification by reduction of the irradiated volume could potentially reduce treatment volume and mean doses to organs at risk. The proposed contouring approach should be studied further in the context of a clinical trial.

Oligometastatic head and neck cancer: Which patients benefit from radical local treatment of all tumour sites?

BACKGROUND: There is a large lack of evidence for optimal treatment in oligometastatic head and neck cancer and it is especially unclear which patients benefit from radical local treatment of all tumour sites. METHODS: 40 patients with newly diagnosed oligometastatic head and neck cancer received radical local treatment of all tumour sites from 14.02.2008 to 24.08.2018. Primary endpoint was overall survival. Time to occurrence of new distant metastases and local control were evaluated as secondary endpoints as well as prognostic factors in univariate und multivariate Cox's regression analysis. To investigate the impact of total tumour volume on survival, all tumour sites were segmented on baseline imaging. RESULTS: Radical local treatment included radiotherapy in 90% of patients, surgery in 25% and radiofrequency ablation in 3%. Median overall survival from first diagnosis of oligometastatic disease was 23.0 months, 2-year survival was 48%, 3-year survival was 37%, 4-year survival was 24% and 5-year survival was 16%. Median time to occurrence of new distant metastases was 11.6 months with freedom from new metastases showing a tail pattern after 3 years of follow-up (22% at 3, 4- and 5-years post-treatment). In multivariate analysis, better ECOG status, absence of bone and brain metastases and lower total tumour volume were significantly associated with improved survival, whereas the number of metastases and involved organ sites was not. CONCLUSIONS: Radical local treatment in oligometastatic head and neck cancer shows promising outcomes and needs to be further pursued. Patients with good performance status, absence of brain and bone metastases and low total tumour volume were identified as optimal candidates for radical local treatment in oligometastatic head and neck cancer and should be considered for selection in future prospective trials.

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.

Influence of Gender on Radiosensitivity during Radiochemotherapy of Advanced Rectal Cancer.

Gender is increasingly recognized as an important factor in medicine, although it has long been neglected in medical research in many areas. We have studied the influence of gender in advanced rectal cancer with a special focus on radiosensitivity. For this purpose, we studied a cohort of 495 men (84.1% ≥ T3, 63.6% N1, 17.6%, M1) and 215 women (84.2% ≥ T3, 56.7% N1, 22.8%, M1) who all suffered from advanced rectal cancer and were treated with radiochemotherapy. The energy deposited, DNA double-strand break (dsb) repair, occurrence of chromosomal aberrations, duration of therapy, tumor regression and tumor-infiltrating lymphocytes, laboratory parameters, quality of life and survival were assessed. The residual DNA dsb damage 24 h after irradiation in lymphocytes was identical in both sexes. Furthermore, chromosomal aberrations accurately reflecting radiosensitivity, were similar in both sexes. There were no gender-dependent differences in tumor regression, tumor-infiltrating lymphocytes and outcome indicating no differences in the radiosensitivity of cancer cells. The irradiated tumor volume in women was slightly lower than in men, related to body weight, no difference was observed. However, when the total energy deposited was calculated and related to the body weight, women were exposed to higher amounts of ionizing radiation. During radiochemotherapy, decreases in blood lymphocyte counts and albumin and several quality-of-life parameters such as nausea and vomiting, loss of appetite, and diarrhea were significantly worse in women. There is no difference in radiation sensitivity between men and women in both normal tissue and tumors. During radiochemotherapy, the quality of life deteriorates more in women than in men. However, women also recover quickly and there are no long-term differences in quality of life.