Assessing the Desmoid-Type Fibromatosis Patients’ Voice: Comparison of Health-Related Quality of Life Experiences from Patients of Two Countries

Desmoid-type fibromatosis (DTF) is a rare, nonmetastasising soft tissue tumour. Symptoms, unpredictable growth, lack of definitive treatments, and the chronic character of the disease can significantly impact health-related quality of life (HRQoL). We aimed at identifying the most important HRQoL issues according to DTF patients in two countries, in order to devise a specific HRQoL questionnaire for this patient group. DTF patients and healthcare providers (HCPs) from the Netherlands and the United Kingdom individually ranked 124 issues regarding diagnosis, treatment, follow-up, recurrence, living with DTF, healthcare, and supportive care experiences, according to their relevance. Descriptive statistics were used to calculate priority scores. The most highly ranked issues by patients (n = 29) were issues concerning “tumour growth,” “feeling that there is something in the body that does not belong there,” and “fear of tumour growth into adjacent tissues or organs” with mean (M) scores of 3.0, 2.9, and 2.8, respectively (Likert scale 1-4). HCPs (n = 31) gave higher scores on most issues compared to patients (M 2.3 vs. M 1.8).

This study evaluates the results of the active surveillance (AS) approach in adult patients with desmoid-type fibromatosis (DTF) because AS is advocated as a front-line approach for DTF in the European consensus guidelines. A systematic literature search was conducted (December 19th, 2019, updated on April 14th, 2020). Studies describing the outcomes of the AS approach were included. The PRISMA guidelines were used. Twenty-five articles were included for data retrieval. Forty-two percent of reported patients (1480 of 3527 patients) received AS, the majority were women and the majority had a primary tumour. The median age at diagnosis ranged from 28 to 59 years. Common tumour sites were the extremities/girdles (n = 273), the abdominal wall (n = 253) and the trunk (n = 153). The median reported percentage of progressive disease, stable disease and partial response was 20% (interquartile range [IQR]: 13-35%), 59% (IQR: 37-69%) and 19% (IQR 3-23%), respectively. In 640 patients, the outcome was not specified. The median reported percentage of shifting to an active form of treatment was 29%, most commonly to systemic treatment (n = 195) and surgery (n = 107). The reported median follow-up time ranged between 8 and 73 months. The reported median time to progression and/or initiation of the subgroup shifting from AS to ‘active’ therapy ranged from 6.3 months to 19.7 months. The majority of patients undergoing AS have either stable disease or a partial response, and about one-third of patients shift to an active form of treatment. Selecting patients who will benefit from active surveillance upfront should be the priority of future studies.

We present a case of a desmoid tumor of the splenic hilum laparoscopically resected in a 70-year-old male with a previous history of chromophobe renal cell carcinoma and ocular spindle melanoma. Although benign, desmoid tumors might be infiltrative and produce serious complications. Treatment remains controversial, ranging from surgery and medical therapies to observation. Management of desmoid-type fibromatoses (DTFs) must be individualized, considering the risk of complications and recurrence.

We aimed at identifying the most important health-related quality of life (HRQoL) issues according to desmoid-type fibromatosis (DTF) patients in two countries, in order to devise a specific HRQoL questionnaire for this patient group. DTF patients and healthcare providers (HCPs) from the Netherlands and the United Kingdom individually ranked 124 issues regarding diagnosis, treatment, follow-up, recurrence, living with DTF, healthcare, and supportive care experiences, according to their relevance. Descriptive statistics were used to calculate priority scores. The most highly ranked issues by patients (n?=?29) were issues concerning ?tumour growth,? ?feeling that there is something in the body that does not belong there,? and ?fear of tumour growth into adjacent tissues or organs? with mean (M) scores of 3.0, 2.9, and 2.8, respectively (Likert scale 1?4). British patients scored higher on most issues compared to Dutch patients (M 2.2 vs. M 1.5). HCPs (n?=?31) gave higher scores on most issues compared to patients (M 2.3 vs. M 1.8). This study identified the most relevant issues for DTF patients, which should be included in a DTF-specific HRQoL questionnaire. Additionally, we identified differences in priority scores between British and Dutch participating patients. Field testing in a large, international cohort is needed to confirm these findings and to devise a comprehensive and specific HRQoL questionnaire for DTF patients.

Pazopanib is a multi-targeted tyrosine kinase inhibitor that is FDA-approved for metastatic soft-tissue sarcomas (STSs) after the first line. We proposed a phase II study evaluating pazopanib as a first-line agent in patients with advanced disease who are deemed not to be candidates for chemotherapy. Eligible patients were at least 18 years old, not candidates for chemotherapy and were treatment naive. Pazopanib was titrated from 200 mg twice daily to a goal of 800 mg daily. The primary end point was the clinical benefit rate (CBR) (CBR = completed response + partial response + stable disease per Response Evaluation Criteria in Solid Tumours [RECIST 1.1]) at 16 weeks. The sample size of 56 evaluable patients was calculated to provide 80% power to test a hypothesised CBR of ò35% against an unfavourable CBR of ó20%. If ò 17 patients achieved benefit, the null CBR of 20% would be rejected at a nominal 5% alpha level. Secondary end points included progression-free survival (PFS), overall survival (OS), quality of life and serum biomarkers. Fifty-six patients were enrolled from May 2015 to February 2019 and are included in the intention-to-treat analysis. Median PFS was 3.67 (2.62-7.25) months. Median OS was 14.16 (95% confidence interval [CI]: 8.4-NR) months, CBR = 39.29% (22/56) (CI = 0.265-0.533, p = 0.0007). No new or unexpected adverse events were seen. The most common grade I-II events were diarrhea, nausea and fatigue. The most common grade III-IV events were hypertension and liver function test abnormalities. These data suggest that there is a benefit to front-line pazopanib in patients with STSs who are not candidates for cytotoxic chemotherapy.

The guideline committee for clinical care of extra-abdominal desmoid-type fibromatosis in Japan conducted a systematic review of treatment with doxorubicin-based chemotherapy for desmoid-type fibromatosis. We searched the pertinent literature. Two reviewers evaluated and screened it independently for eligibility and extracted data. They rated each report according to the grading of recommendations development and evaluation methodology. Based on the ‘body of evidence’, which the reviewers created, the clinical guideline committee decided a recommendation for the clinical question, ‘Is doxorubicin-based chemotherapy effective for patients with extra-abdominal desmoid-type fibromatosis? Fifty-three articles were extracted by the literature search, and one from hand search. After the first and second screenings, five articles were subjected to the final evaluation. There were no randomized controlled trials. According to response evaluation criteria in solid tumors criteria, the response rates of doxorubicin-based regimens and liposomal doxorubicin were 44% (28.6-54) and 33.3% (0-75) on average, respectively. In two reports, the response rates of doxorubicin-based regimens were higher than those of non-doxorubicin-based ones; 54% vs 12%, 40% vs 11%, respectively. The rates of G3 or G4 complications according to common terminology criteria for adverse events were 28% and 13% with doxorubicin-based and liposomal doxorubicin chemotherapy, respectively, including neutropenia or cardiac dysfunction. None of the reports addressed the issue of QOL. Although the evidence level was low in the evaluated studies, doxorubicin-based and liposomal doxorubicin chemotherapy was observed to be effective. However, doxorubicin-based chemotherapy is associated with non-ignorable adverse events, and is not covered by insurance in Japan. We weakly recommend doxorubicin-based chemotherapy for patients with extra-abdominal desmoid-type fibromatosis in cases resistant to other treatments.