3.1 Study population
The sociodemographic and disease-related characteristics of the study populations are shown in Table 1.
Table 1
Sociodemographic and disease-related characteristics of the study populations [n (%)]
| Breast cancer | Multiple myeloma | Prostate cancer |
Number of patients | 101 | 107 | 66 |
Study center CIO Bonn Johanniter Hospital Bonn University Hospital Dresden | 80 (79.2) 21 (20.8) 0 (0) | 35 (32.7) 12 (11.2) 60 (56.1) | 6 (9.1) 0 (0) 60 (90.9) |
Gender Male Female | 0 (0) 101 (100) | 67 (62.6) 40 (37.4) | 66 (100) 0 (0) |
Age Median [years] | 58 (IQR: 16, range: 28–84, mean 58.0, SD 11.4) | 62 (IQR: 13, range: 33–83, mean: 62.0, SD: 9.1) | 76 (IQR: 8, range: 59–94, mean: 74.5, SD: 6.9) |
Time since the first diagnosis of cancer Median [months] | 14 (IQR: 67, range: 1–506, mean: 59, SD: 86.9) | 59 (IQR: 69, range: 2–255, mean: 63.7, SD: 52.8) | 27 (IQR: 60, range: 1–190, mean: 41.7, SD: 43.3) |
Current therapy situation Outpatient therapy Inpatient therapy | 101 (100) 0 (0) | 87 (81.3) 20 (18.7) | 56 (84.9) 10 (15.1) |
Current therapy intention Curative Palliative Other/unknown Therapy sequence Adjuvant Neoadjuvant Other/unknown | 32 (31.7) 53 (52.5) 16 (15.8) 52 (51.5) 23 (22.8) 26 (25.7) | 35 (32.7) 68 (63.6) 4 (3.7) n.a. n.a. n.a. | 24 (36.4) 30 (45.5) 12 (18.2) 3 (4.5) 0 (0) 63 (95.5) |
Metastases Patients with metastases Number of metastases per patient | 54 (53.5) 0.9 (SD: 0.9, median: 1, IQR: 1, range: 0–4) | n.a. n.a. | 20 (30.3) 0.3 (SD: 0.5, median: 0, IQR: 1, range: 0–2) |
Relapses Patients with relapse | 22 (21.8) | 27 (25.2) | 18 (27.3) |
n.a. = not applicable, IQR = interquartile range, SD = standard deviation |
53.5% (n = 54) of the breast cancer patients had metastases. The most often occurring metastases were located in bones (n = 34), liver (n = 20), and lung (n = 15). 22 patients (21.8%) had a relapse of their disease. 15 of them had only one relapse. An estrogen receptor-positive disease occurred in 65 patients (64.4%). Progesterone receptor-positive were 46 patients (45.6%) and HER2-positive 44 patients (43.6%).
25.2% (n = 27) of the multiple myeloma patients had a relapse of their disease. 22 of them had only one relapse. 14 patients (13.1%) were currently undergoing autologous stem cell transplantation (SCT). 77 patients (72.0%) received at least one autologous SCT during former therapy lines.
30.3% (n = 20) of the prostate cancer patients had metastases. With one exception the metastases were located in bones (n = 20). 18 patients (27.3%) had a relapse of their disease. Most patients belonged to the high-risk Gleason grade group 5 (n = 26, 39.4%).
The used drug classes for the three tumor entities are shown in Fig. 2. Overall, the mean number of anticancer drugs per patient was 7.7 (SD: 4.1, median: 7, IQR: 5, range 0–24) in the multiple myeloma patients, followed by the breast cancer patients with a mean of 5.8 (SD: 3.4, median: 5, IQR: 4, range: 0–17). The prostate cancer patients received only a mean of 1.9 (SD: 1.6, median: 2, IQR: 1, range 0–7) drugs per patient.
The most used anticancer drugs in breast cancer patients were trastuzumab (n = 91, 15.7%), cyclophosphamide (n = 69, 11.9%), epirubicin (n = 68, 11.7%), pertuzumab (n = 55, 9.5%), and docetaxel (n = 44, 7.6%). The most used drugs in multiple myeloma patients were dexamethasone (n = 199, 24.1%), bortezomib (n = 124, 15.0%), cyclophosphamide (n = 113, 13.7%), melphalan (n = 111, 13.4%), and lenalidomide (n = 110, 13.3%). The most used drugs in prostate cancer patients were not further specified LH-RH analogs (n = 32, 25.4%), bicalutamide (n = 24, 19.1%), leuprorelin (n = 23, 18.3%), degarelix (n = 12, 9.5%), and abiraterone acetate (n = 10, 7.9%).
Breast cancer patients were treated for a mean of 1.7 indications for supportive care (SD: 1.7, median: 1, IQR: 1, range: 0–6). They received most frequently care for nausea and emesis (n = 41, 24.3%), bone complications (n = 40, 23.7%), and gastric ulcer prophylaxis (n = 18, 10.7%). Multiple myeloma patients were treated also for a mean of 1.7 supportive care indications (SD: 1.5, median: 1, IQR: 2, range: 0–6), most frequently for bone complications (n = 48, 26.5%), gastric ulcer prophylaxis (n = 43, 23.8%), and pain (n = 34, 18.8%). Prostate cancer patients were only treated for a mean of 0.4 supportive care indications (SD: 0.9, median: 0, IQR: 0, range: 0–4), the most frequently for bone complications (n = 7, 25.9%), gastric ulcer prophylaxis (n = 6, 22.2%), and pain (n = 5, 18.5%).
3.2 Completion of questionnaires
Missing values occurred if patients did not answer a question at all or not clear enough by marking an answer on the paper-based questionnaires. Within the 101 questionnaires filled in by the breast cancer patients, the questions regarding the prevalence of the symptoms were not answered in 2.2% of cases (mean number of cases 2.2, SD 3.17, range 0–16). The questions about the importance of the symptoms were not answered in 4.2% of cases (mean number of cases 4.2, SD 1.52, range 1–10). For the 107 questionnaires of the multiple myeloma patients, the missing values amount to 0.8% of cases (mean number of cases 0.9, SD 1.38, range 0–6) for the prevalence questions and 1.6% of cases (mean number of cases 1.7, SD 1.29, range 0–6) for the importance questions. For the 66 questionnaires of the prostate cancer patients, the missing values amount to 0.2% of cases (mean number of cases 0.1, SD 0.31, range 0–1) for the prevalence questions and 5.6% of cases (mean number of cases 3.7, SD 1.77, range 1–7) for the importance questions.
3.4 Symptom ranking and item set compilation
For each of the three tumor diseases, the symptoms were ranked according to their combined prevalence-importance (P-I) score. Then, the symptoms with the lowest scores indicating high prevalence and importance for the respective tumor disease were compiled to an item set until a maximum of 40 PRO-CTCAE items was reached. The final PRO-CTCAE item set for breast cancer included 39 items related to 21 symptoms, for multiple myeloma 39 items related to 19 symptoms, and for prostate cancer 40 items related to 19 symptoms, respectively. A comparison of the three tumor disease-specific PRO-CTCAE item sets ranked by their combined P-I scores is shown in Table 2. The three individual PRO-CTCAE item sets are shown in the Supplementary Information.
Table 2
Comparison of the tumor entity-specific PRO-CTCAE item sets according to the combined prevalence-importance (P-I) scores of the symptoms
Breast cancer | Combined P-I score | Multiple myeloma | Combined P-I score | Prostate cancer | Combined P-I score |
Fatigue#§ | 3 | Fatigue#§ | 4 | Insomnia#§ | 9 |
Numbness and tingling§ | 9 | Numbness and tingling§ | 6 | Urinary frequency | 9 |
Nausea§ | 16 | General pain#§ | 11 | Achieve and maintain erection | 9 |
Muscle pain# | 19 | Insomnia#§ | 12 | Urinary incontinence | 10 |
Insomnia#§ | 23 | Nausea§ | 15 | Ejaculation | 10 |
Hair loss | 24 | Shortness of breath#§ | 19 | Fatigue#§ | 11 |
Joint pain# | 24 | Hair loss | 20 | Urinary urgency | 12 |
Blurred vision | 27 | Joint pain# | 21 | Unable to have orgasm | 16 |
Concentration§ | 28 | Diarrhea§ | 24 | Joint pain# | 21 |
General pain#§ | 30 | Muscle pain# | 25 | Anxious§ | 19 |
Diarrhea§ | 33 | Anxious§ | 25 | Decreased libido | 21 |
Constipation§ | 34 | Decreased appetite§ | 30 | General pain#§ | 27 |
Taste changes | 35 | Swelling | 37 | Hot flashes | 28 |
Dizziness# | 36 | Dizziness# | 37 | Swelling# | 32 |
Shortness of breath#§ | 37 | Heart palpitations | 38 | Shortness of breath#§ | 37 |
Heart palpitations | 44 | Concentration§ | 39 | Sad§ | 37 |
Memory | 44 | Constipation§ | 43 | Muscle pain# | 40 |
Swelling# | 45 | Taste changes | 47 | Painful urination | 41 |
Rash | 46 | Mouth/throat sores§ | 49 | Dizziness# | 45 |
Nail ridging+ | 47 | | | | |
Nail discoloration+ | 47 | | | | |
#: Part of all three PRO-CTCAE item sets;BOLD: Part of only one PRO-CTCAE item set; §: Part of the PRO-CTCAE core item set; +: Symptoms were combined in the patient questionnaire |
Eight symptoms are included in all three item sets. The symptoms with the highest rankings across the item sets were “Fatigue” and “Insomnia”. Symptoms with the highest rankings included in only one item set were symptoms affecting the urogenital system in the prostate cancer item set, “Blurred vision” in the breast cancer item set and “Decreased appetite” in the multiple myeloma item set.