conflict of interest with AstraZeneca (research funding); MSD (research funding). (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, “type”:”clinical-trial”,”attrs”:”text”:”NCT03453892″,”term_id”:”NCT03453892″NCT03453892. Registered on 05 March 2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08006-0. Standard deviation, Immunotherapy, Radiotherapy, Central nervous system, Programmed death ligand, Head and neck squamous cell carcinoma, Non small cell lung carcinoma Incidence and grades of irAE Twenty-nine out of one hundred four surveyed patients developed any irAE (Table?2). The median time from first drug administration to the endpoint clinician-reported irAE was 2.3?months. Hypothyroidism was the most frequent one (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), pneumonitis (3%), and other irAE (5%). According to CTCAE 25 patients (24%) were classified to grade 1C2 reactions while four patients (4%) developed grade 3 irAE. No grade 4 and 5 events were observed. All cases of hypothyroidism and hepatitis were confirmed by laboratory tests, skin reactions were evaluated clinically, all instances of pneumonitis were confirmed by CT scan. Colonoscopy in case of diarrhoea was not required. In five individuals irAE led to immunotherapy treatment interruption and in six individuals to long term discontinuation. In the two individuals with pre-existing autoimmune diseases, one patient with psoriasis experienced a disease flare and one patient with Hashimotos thyroiditis in the hypothyroid stage experienced no irAE. As mentioned above, some individuals received radiotherapy in addition to immunotherapy. In order to clarify that irAE in these individuals are no local radiotherapy effects, these instances are summarized in supplementary Table?1. Table 2 Immune-related adverse events Immune-related adverse event. No grade 4 and 5 events were observed Patient irAE screening questionnaire A total of 784 questionnaires were collected. Out of the 104 surveyed individuals, 96 individuals (92%) completed at least one questionnaire. The median quantity of completed questionnaires per individual was 6 (range 0C40). Number?2a-h depicts the percentage for each question that was positively answered separately for patients with no current clinician-reported irAE, for patients with current clinician-reported irAE, and for those with current clinician-reported irAE related to the organ-specific panel. Open in a separate windowpane Fig. 2 Rate of recurrence of positive answers of the ST-ICI cohort depending on clinician-reported irAE. a Gastrointestinal irAE. b Pulmonary irAE. c Endocrine irAE. d Pores and skin irAE. e Hepatic irAE. f Neurologic irAE. g Renal irAE. h Non-specific irAE Clinician-reported gastrointestinal irAE were recognized by different questions at a rate of 50% as feeling unwell, nausea or vomiting, differing bowel movements, nocturnal defecation, thin or foul-smelling stool, abdominal pain and bloody or mucous stool (Fig.?2a). Questions on loss of hunger, painful defecation or abdominal cramps did not correlate with gastrointestinal irAE. Clinician-reported pulmonary irAE were detected at a rate of 50% from the questions shortness ATB-337 of breath and difficulty in breathing (Fig. ?(Fig.2b).2b). Individuals with pulmonary irAE, i.e. pneumonitis, did not report suffering from increased coughing and mucous sputum. Clinician-reported endocrine irAE ATB-337 were recognized in at least 50% of instances by the query on sleeping disorders. The query on fatigue improved in endocrine irAE to 70%, whereas it was also answered positively in 49% of individuals without irAE (Fig. ?(Fig.2c).2c). Questions on exhaustion, dizziness, excessive thirst, libido changes or palpitations did not determine endocrine irAE. Clinician-reported pores and skin irAE were recognized at a rate of 50% from the questions pores and skin rash, itchiness and deterioration of pores and skin diseases, whereas the query hair loss was not increased in pores and skin irAE (Fig. ?(Fig.2d).2d). Hepatic irAE were not detected, neither from the query yellowing of pores and skin or eyes nor the query on painful top right belly (Fig. ?(Fig.2e).2e). The questionnaire also contained a neurologic and renal query panel, whereas no neurologic irAE (Fig. ?(Fig.2f)2f) and no renal irAE (Fig. ?(Fig.2g)2g).There exists a mild correlation between a reduction of quality of life during radiochemotherapy and prolonged survival, which is probably a marker for treatment intensity [36]. were collected. A total of 29 irAE were reported by clinicians. The most frequent irAE was hypothyroidism (9%), followed by pores and skin reactions (5%), hepatitis (4%), diarrhea (3%), and pneumonitis (3%). Questions that became a lot more frequently positive at period factors of clinician-reported irAE had been weight change, problems to grip stuff, bloody or mucous feces and sleeplessness. Self-reported organ-specific queries discovered at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and epidermis irAE. It had been extremely hard to identify hepatic irAE using the questionnaire. Bottom line Questionnaires can help identify gastrointestinal, lung, endocrine, or epidermis irAE, however, not hepatic irAE. Queries on weight transformation and insomnia can help to improve the detection price of irAE, besides organ-specific queries. These email address details are a very important contribution to the near future development of a particular and practicable questionnaire for early self-reported recognition of irAE during ICI therapy in cancers sufferers. Trial enrollment ClinicalTrials.gov, “type”:”clinical-trial”,”attrs”:”text”:”NCT03453892″,”term_id”:”NCT03453892″NCT03453892. Registered on 05 March 2018. Supplementary Details The online edition contains supplementary materials offered by 10.1186/s12885-021-08006-0. Regular deviation, Immunotherapy, Radiotherapy, Central anxious system, Programmed loss of life ligand, Mind and throat squamous cell carcinoma, Non little cell lung carcinoma Levels and Occurrence of irAE Twenty-nine out of 1 hundred four surveyed sufferers created any irAE (Desk?2). The median period from first medication administration towards the endpoint clinician-reported irAE was 2.3?a few months. Hypothyroidism was the most typical one (9%), accompanied by epidermis reactions (5%), hepatitis (4%), diarrhea (3%), pneumonitis (3%), and various other irAE (5%). Regarding to CTCAE 25 sufferers (24%) were categorized to quality 1C2 reactions while four sufferers (4%) developed quality 3 irAE. No quality 4 and 5 occasions were noticed. All situations of hypothyroidism and hepatitis had been confirmed by lab tests, epidermis reactions were examined clinically, all situations of pneumonitis had been verified by CT scan. Colonoscopy in case there is diarrhoea had not been necessary. In five sufferers irAE resulted in immunotherapy treatment interruption and in six sufferers to long lasting discontinuation. In both sufferers with pre-existing autoimmune illnesses, one individual with psoriasis experienced an illness flare and one individual with Hashimotos thyroiditis in the hypothyroid stage experienced no irAE. As stated above, some sufferers received radiotherapy furthermore to immunotherapy. To be able to clarify that irAE in these sufferers are no regional radiotherapy results, these situations are summarized in supplementary Desk?1. Desk 2 Immune-related adverse occasions Immune-related adverse event. No quality 4 and 5 occasions were observed Individual irAE testing questionnaire A complete of 784 questionnaires had been collected. From the 104 surveyed sufferers, 96 sufferers (92%) finished at least one questionnaire. The median variety of finished questionnaires per affected individual was 6 (range 0C40). Amount?2a-h depicts the percentage for every question that was positively answered separately for individuals without current clinician-reported irAE, for individuals with current clinician-reported irAE, and for all those with current clinician-reported irAE linked to the organ-specific -panel. Open in another screen Fig. 2 Regularity of positive answers from the ST-ICI cohort based on clinician-reported irAE. a Gastrointestinal irAE. b Pulmonary irAE. c Endocrine irAE. d Epidermis irAE. e Hepatic irAE. f Neurologic irAE. g Renal irAE. h nonspecific irAE Clinician-reported gastrointestinal irAE had been discovered by different queries for a price of 50% as sense unwell, nausea / vomiting, differing bowel motions, nocturnal defecation, slim or foul-smelling feces, abdominal discomfort and bloody or mucous feces (Fig.?2a). Queries on lack of urge for food, unpleasant defecation or abdominal cramps didn’t correlate with gastrointestinal irAE. Clinician-reported pulmonary irAE had been detected for a price of 50% with the queries shortness of breathing and problems in inhaling and exhaling (Fig. ?(Fig.2b).2b). Sufferers with pulmonary irAE, we.e. pneumonitis, didn’t Rabbit polyclonal to ZNF404 report experiencing increased hacking and coughing and mucous sputum. Clinician-reported endocrine irAE had been determined in at least 50% of situations by the issue on sleeplessness. The issue on fatigue elevated in endocrine irAE to 70%,.Signed up on 05 March 2018. Supplementary Information The web version contains supplementary material offered by 10.1186/s12885-021-08006-0. Regular deviation, Immunotherapy, Radiotherapy, Central anxious system, Programmed death ligand, Head and neck squamous cell carcinoma, Non little cell lung carcinoma Incidence and levels of irAE Twenty-nine out of 1 hundred four surveyed sufferers developed any irAE (Desk?2). irAE had been weight change, problems to grip factors, bloody or mucous feces and sleeplessness. Self-reported organ-specific queries discovered at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and epidermis irAE. It had been extremely hard to identify hepatic irAE using the questionnaire. Bottom line Questionnaires can help identify gastrointestinal, lung, endocrine, or epidermis irAE, however, not hepatic irAE. Queries on weight modification and insomnia can help to improve the detection price of irAE, besides organ-specific queries. These email address details are a very ATB-337 important contribution to the near future development of a particular and practicable questionnaire for early self-reported recognition of irAE during ICI therapy in tumor sufferers. Trial enrollment ClinicalTrials.gov, “type”:”clinical-trial”,”attrs”:”text”:”NCT03453892″,”term_id”:”NCT03453892″NCT03453892. Registered on 05 March 2018. Supplementary Details The online edition contains supplementary materials offered by 10.1186/s12885-021-08006-0. Regular deviation, Immunotherapy, Radiotherapy, Central anxious system, Programmed loss of life ligand, Mind and throat squamous cell carcinoma, Non little cell lung carcinoma Occurrence and levels of irAE Twenty-nine out of 1 hundred four surveyed sufferers created any irAE (Desk?2). The median period from first medication administration towards the endpoint clinician-reported irAE was 2.3?a few months. Hypothyroidism was the most typical one (9%), accompanied by epidermis reactions (5%), hepatitis (4%), diarrhea (3%), pneumonitis (3%), and various other irAE (5%). Regarding to CTCAE 25 sufferers (24%) were categorized to quality 1C2 reactions while four sufferers (4%) developed quality 3 irAE. No quality 4 and 5 occasions were noticed. All situations of hypothyroidism and hepatitis had been confirmed by lab tests, epidermis reactions were examined clinically, all situations of pneumonitis had been verified by CT scan. Colonoscopy in case there is diarrhoea had not been obligatory. In five sufferers irAE resulted in immunotherapy treatment interruption and in six sufferers to long lasting discontinuation. In both sufferers with pre-existing autoimmune illnesses, one individual with psoriasis experienced an illness flare and one individual with Hashimotos thyroiditis in the hypothyroid stage experienced no irAE. As stated above, some sufferers received radiotherapy furthermore to immunotherapy. To be able to clarify that irAE in these sufferers are no regional radiotherapy results, these situations are summarized in supplementary Desk?1. Desk 2 Immune-related adverse occasions Immune-related adverse event. No quality 4 and 5 occasions were observed Individual irAE testing questionnaire A complete of 784 questionnaires had been collected. From the 104 surveyed sufferers, 96 sufferers (92%) finished at least one questionnaire. The median amount of finished questionnaires per affected person was 6 (range 0C40). Body?2a-h depicts the percentage for every question that was positively answered separately for individuals without current clinician-reported irAE, for individuals with current clinician-reported irAE, and for all those with current clinician-reported irAE linked to the organ-specific -panel. Open in another home window Fig. 2 Regularity of positive answers from the ST-ICI cohort based on clinician-reported irAE. a Gastrointestinal irAE. b Pulmonary irAE. c Endocrine irAE. d Skin irAE. e Hepatic irAE. f Neurologic irAE. g Renal irAE. h Non-specific irAE Clinician-reported gastrointestinal irAE were detected by different questions at a rate of 50% as feeling unwell, nausea or vomiting, differing bowel movements, nocturnal defecation, thin or foul-smelling stool, abdominal pain and bloody or mucous stool (Fig.?2a). Questions on loss of appetite, painful defecation or abdominal cramps did not correlate with gastrointestinal irAE. Clinician-reported pulmonary irAE were detected at a rate of 50% by the questions shortness of breath and difficulty in breathing (Fig. ?(Fig.2b).2b). Patients with pulmonary irAE, i.e. pneumonitis, did not report suffering from increased coughing and mucous sputum. Clinician-reported endocrine irAE were identified in at least 50% of cases by the question on insomnia. The question on fatigue increased in endocrine irAE to 70%, whereas it was also answered positively in 49% of patients without irAE (Fig. ?(Fig.2c).2c). Questions on exhaustion, dizziness, excessive thirst, libido changes or palpitations did not identify endocrine irAE. Clinician-reported skin irAE were detected at a rate of 50% by the questions skin rash, itchiness and deterioration of skin diseases, whereas the question hair loss was not increased in skin irAE (Fig. ?(Fig.2d).2d). Hepatic irAE were not detected, neither by the question yellowing of skin or eyes nor the question on painful upper right abdomen (Fig. ?(Fig.2e).2e). The questionnaire also contained a neurologic and renal question panel, whereas no neurologic irAE (Fig..Endocrine irAE include thyroid dysfunction, hypophysitis, diabetes mellitus, and primary adrenal insufficiency. 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, “type”:”clinical-trial”,”attrs”:”text”:”NCT03453892″,”term_id”:”NCT03453892″NCT03453892. Registered on 05 March 2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08006-0. Standard deviation, Immunotherapy, Radiotherapy, Central nervous system, Programmed death ligand, Head and neck squamous cell carcinoma, Non small cell lung carcinoma Incidence and grades of irAE Twenty-nine out of one hundred four surveyed patients developed any irAE (Table?2). The median time from first drug administration to the endpoint clinician-reported irAE was 2.3?months. Hypothyroidism was the most frequent one (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), pneumonitis (3%), and other irAE (5%). According to CTCAE 25 patients (24%) were classified to grade 1C2 reactions while four patients (4%) developed grade 3 irAE. No grade 4 and 5 events were observed. All cases of hypothyroidism and hepatitis were confirmed by laboratory tests, pores and skin reactions were evaluated clinically, all instances of pneumonitis were confirmed by CT scan. Colonoscopy in case of diarrhoea was not required. In five individuals irAE led to immunotherapy treatment interruption and in six individuals to long term discontinuation. In the two individuals with pre-existing autoimmune diseases, one patient with psoriasis experienced a disease flare and one patient with Hashimotos thyroiditis in the hypothyroid stage experienced no irAE. As mentioned above, some individuals received radiotherapy in addition to immunotherapy. In order to clarify that irAE in these individuals are no local radiotherapy effects, these instances are summarized in supplementary Table?1. Table 2 Immune-related adverse events Immune-related adverse event. No grade 4 and 5 events were observed Patient irAE screening questionnaire A total of 784 questionnaires were collected. Out of the 104 surveyed individuals, 96 individuals (92%) completed at least one questionnaire. The median quantity of completed questionnaires per individual was 6 (range 0C40). Number?2a-h depicts the percentage for each question that was positively answered separately for patients with no current clinician-reported irAE, for patients with current clinician-reported irAE, and for those with current clinician-reported irAE related to the organ-specific panel. Open in a separate windows Fig. 2 Rate of recurrence of positive answers of the ST-ICI cohort depending on clinician-reported irAE. a Gastrointestinal irAE. b Pulmonary irAE. c Endocrine irAE. d Pores and skin irAE. e Hepatic irAE. f Neurologic irAE. g Renal irAE. h Non-specific irAE Clinician-reported gastrointestinal irAE were recognized by different questions at a rate of 50% as feeling unwell, nausea or vomiting, differing bowel movements, nocturnal defecation, thin or foul-smelling stool, abdominal pain and bloody or mucous stool (Fig.?2a). Questions on loss of hunger, painful defecation or abdominal cramps did not correlate with gastrointestinal irAE. Clinician-reported pulmonary irAE were detected at a rate of 50% from the questions shortness of breath and difficulty in breathing (Fig. ?(Fig.2b).2b). Individuals with pulmonary irAE, i.e. pneumonitis, did not report suffering from increased coughing and mucous sputum. Clinician-reported endocrine irAE were recognized in at least 50% of instances by the query on insomnia. The query on fatigue improved.This may have encouraged them to report their symptoms to the physician and increased the correlation between patient- and clinician-reported irAE. 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 pores and 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 items, bloody or mucous stool and sleeping disorders. Self-reported organ-specific questions recognized at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and pores and skin irAE. It was not possible to detect hepatic irAE with the questionnaire. Summary Questionnaires can help to detect gastrointestinal, lung, endocrine, or pores and skin irAE, but not hepatic irAE. Questions on weight switch 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 malignancy individuals. Trial sign up ClinicalTrials.gov, “type”:”clinical-trial”,”attrs”:”text”:”NCT03453892″,”term_id”:”NCT03453892″NCT03453892. Registered on 05 March 2018. Supplementary Info The online version contains supplementary material available at 10.1186/s12885-021-08006-0. Standard deviation, Immunotherapy, Radiotherapy, Central nervous system, Programmed death ligand, Head and neck squamous cell carcinoma, Non small cell lung carcinoma Incidence and marks of irAE Twenty-nine out of one hundred four surveyed patients developed any irAE (Table?2). The median time from first drug administration to the endpoint clinician-reported irAE was 2.3?months. Hypothyroidism was the most frequent one (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), pneumonitis (3%), and other irAE (5%). According to CTCAE 25 patients (24%) were classified to grade 1C2 reactions while four patients (4%) developed grade 3 irAE. No grade 4 and 5 events were observed. All cases of hypothyroidism and hepatitis were confirmed by laboratory tests, skin reactions were evaluated clinically, all cases of pneumonitis were confirmed by CT scan. Colonoscopy in case of diarrhoea was not mandatory. In five patients irAE led to immunotherapy treatment interruption and in six patients to permanent discontinuation. In the two patients ATB-337 with pre-existing autoimmune diseases, one patient with psoriasis experienced a disease flare and one patient with Hashimotos thyroiditis in the hypothyroid stage experienced no irAE. As mentioned above, some patients received radiotherapy in addition to immunotherapy. In order to clarify that irAE in these patients are no local radiotherapy effects, these cases are summarized in supplementary Table?1. Table 2 Immune-related adverse events Immune-related adverse event. No grade 4 and 5 events were observed Patient irAE screening questionnaire A total of 784 questionnaires were collected. Out of the 104 surveyed patients, 96 patients (92%) completed at least one questionnaire. The median number of completed questionnaires per patient was 6 (range 0C40). Physique?2a-h depicts the percentage for each question that was positively answered separately for patients with no current clinician-reported irAE, for patients with current clinician-reported irAE, and for those with current clinician-reported irAE related to the organ-specific panel. Open in a separate windows Fig. 2 Frequency of positive answers of the ST-ICI cohort depending on clinician-reported irAE. a Gastrointestinal irAE. b Pulmonary irAE. c Endocrine irAE. d Skin irAE. e Hepatic irAE. f Neurologic irAE. g Renal irAE. h Non-specific irAE Clinician-reported gastrointestinal irAE were detected by different questions at a rate of 50% as feeling unwell, nausea or vomiting, differing bowel movements, nocturnal defecation, thin or foul-smelling stool, abdominal pain and bloody or mucous stool (Fig.?2a). Questions on loss of appetite, painful defecation or abdominal cramps did not correlate with gastrointestinal irAE. Clinician-reported pulmonary irAE were detected at a rate of 50% by the questions shortness of breath and difficulty.