Developing knowledge, attitude and practice questionnaire in desmoid tumours (KAPID study): applying e-Delphi to rare diseases

Background: Rare diseases are associated with unique challenges encountered in diagnosis, treatment and conduct of clinical research. Desmoid tumour (DT) is one such ultra-rare malignancy about which awareness among medical professionals remains limited. We developed a questionnaire to assess knowledge, attitude and practice (KAP) among medical professionals on DT.

Methods: E-Delphi method was used for the assessment of KAP for DT amongst clinical experts (experience of >/= 3 years in DT). 22 open-ended statements were developed by the core research group using current consensus guidelines. In round 1, experts provided subjective feedback which was incorporated into a 35-item questionnaire. Round 2 entailed experts giving feedback as a 5-point Likert scale classified into agreement (median score >/=4), neutral (median score 3) and disagreement (median score <3). Feedback from Round 2 was incorporated and questions with neutral consensus were modified. Questions in Round 3 achieved consensus if >/= 75% participants agreed.

Results: 11 (64.7%) of 17 contacted experts responded in Round 1 including 6 (54.4%) who gave additional inputs and 5 (45.6%) who agreed to all statements. In round 2, 8 out of 11 experts responded to the 35-item questionnaire on knowledge (n = 16), attitude (n = 8) and practice (n = 11). 32 questions obtained agreement and 3 (8.5%) had neutral consensus. These were modified for round 3, in which consensus on 2 (66.6%) was attained. The final questionnaire comprises 34 items with 15, 8 and 11 questions on in the sections of knowledge, attitude and practice (KAP), respectively.

Objectives: Because size-based imaging criteria poorly capture biologic response in desmoid-type fibromatosis (DF), changes in MRI T2 signal intensity are frequently used as a response surrogate, but remain qualitative. We hypothesized that absolute quantification of DF T2 relaxation time derived from parametric T2 maps would be a feasible and effective imaging biomarker of disease activity.

Methods: This IRB-approved retrospective study included 11 patients with DF, managed by observation or systemic therapy, assessed by 3T MRI. Tumor maximum diameter, volume, and T2-weighted signal intensity were derived from manual tumor segmentations. Tumor:muscle T2 signal ratios were recorded. Two readers measured tumor T2 relaxation times using a commercial T2 scanning sequence, manual ROI delineation and commercial calculation software enabling estimation of reader reliability. Objective response rates based on RECIST1.1 and best responses were compared between size-based and signal-based parameters.

Results: Median patient age was 52.6 years; 8 subjects were female (73%). Nine patients with longitudinal assessments were followed for an average of 314 days. Median baseline tumor diameter was 7.2 cm (range 4.4 – 18.2 cm). Median baseline T2 was 65.1 ms (range 40.4 – 94.8 ms, n=11); median at last follow-up was 44.3 ms (-32% from baseline; range 29.3 – 94.7 ms, n=9). T2 relaxation times correlated with tumor:muscle T2 signal ratios, Spearman p=0.78 (p<0.001). T2 mapping showed high inter-reader reliability, ICC=0.84. The best response as a percentage change in T2 values was statistically significant (mean -17.9%, p=0.05, paired t-test) while change in diameter was not (mean -8.9%, p=0.12). Conclusions: Analysis of T2 relaxation time maps of DF may offer a feasible quantitative biomarker for assessing the extent of response to treatment. This approach may have high inter-reader reliability.

Desmoid fibromatosis of the breast (also known as desmoid tumor of the breast) is a rare entity infrequently encountered by oncologists and surgeons caring for patients with breast disease. The current body of literature is highly reliant on case series and extrapolations from other sites of desmoid tumor-related disease. Much remains unclear regarding the pathological origins, natural history, and response to treatment of this condition. Traditional treatment strategies have centered on surgical resection, which may result in significantly disfiguring cosmetic and functional outcomes, frequent need for re-operation, and associated morbidity. There are limited data to support the superiority of upfront surgical resection when compared to medical therapy or watchful waiting strategies. Current treatment guidelines for desmoid tumors do not focus on the breast as a site of disease and are purposefully ambiguous due to the paucity of evidence available. We aim to review the literature concerning desmoid fibromatosis of the breast and propose an algorithm for current evidence-based management of this rare disease in the context of our experience with this pathology at a high-volume quaternary referral center.

Fibromatoses are a heterogeneous group of benign proliferating fibroblasts and myofibroblasts which have a high predilection for recurrence and local invasion, especially deep fibromatoses or desmoid fibromatosis. 18F-FDG PET/CT, the workhorse of oncological imaging in nuclear medicine, can be employed to figure out the nature and aggressiveness of the lesions and various sites of involvement and to monitor treatment response to systemic therapies like tyrosine kinase inhibitors in case of deep or desmoid fibromatoses which is shown in the current research work.

Purpose: Desmoid fibromatosis (DF) is a locally aggressive tumor with low mortality but significant morbidity. There is a lack of standard of care, and existing therapies are associated with significant barriers including access, cost, and toxicities. This study aimed to explore the efficacy and safety of the metronomic therapy (MT) in DF in a large, homogenous cohort from India.

Patients and methods: This study involved histologically confirmed DF cases treated with MT comprising vinblastine (6 mg) and methotrexate (15 mg) both once a week, and tamoxifen (40 mg/m2) in two divided doses once daily between 2002 and 2018.

Results: There were 315 patients with a median age of 27 years; the commonest site was extremity (142 of 315; 45.0%). There were 159 (50.1%) male patients. Of the 123 (39.0%) prior treated patients, 119 had surgery. Of 315 patients, 263 (83.5%) received treatment at our institute (MT-151, 77-local treatment, 9-tyrosine kinase inhibitor, and 26 were observed). Among the MT cohort (n = 163, 61.2%), at a median follow-up of 36 (0.5-186) months, the 3-year progression-free and overall survival were 81.1% (95% CI, 74.3 to 88.4) and 99.2% (95% CI, 97.6 to 100), respectively. There were 35% partial responses. Ninety-two patients (56.4%) completed 1-year therapy, which was an independent prognosticator (P < .0001; hazard ratio, 0.177 [95% CI, 0.083 to 0.377]). MT was well tolerated. Predominant grade ≥3 toxicities were febrile neutropenia, 12 (7.4%) without any chemotoxicity-related death. The annual cost of MT was $130 US dollars.