Recurrent Desmoid Tumor Research Articles

Active surveillance and emerging medical treatment options for desmoid: when and for whom?

This article discusses the evolving approaches to desmoid tumors management, shedding light on recent developments. Active surveillance has become the primary approach for managing primary peripheral desmoid tumors. This strategy was initially based on evidence from retrospective studies. Roughly 50% of cases managed with active surveillance show spontaneous stabilization or regression. Recent prospective trials conducted in Italy, The Netherlands, and France (2022-2023) confirm the efficacy of active surveillance, revealing 3-year progression-free survival rates ranging from 53.4 to 58%. For the patients under active surveillance, decisions regarding treatment are based on significant tumor growth or progressive symptoms. Moreover, three contemporary randomized trials investigated medical treatments for progressive or recurrent desmoid tumors. Sorafenib, pazopanib, and nirogacestat demonstrated clinical activity, as evidenced by favorable progression-free survival and objective response rates. Active surveillance has solidified its position as the primary management approach for desmoid tumors, validated by three robust prospective studies. Three recent randomized trials explored medical treatment for progressive or recurrent desmoid tumors, revealing promising clinical activities.

Abstract PO4-21-01: Recurrent Desmoid Tumor and Ductal Carcinoma In Situ in an African-American Woman: A Case Report and Discussion on Disparities for These Two Cancer Subtypes

Abstract Introduction: Disparities in cancer care in patients from different races and ethnicities unfortunately do exist and are well described in literature. Hormonal-driven cancers, such as some soft-tissue tumors and DCIS, have been demonstrated to impact African-American women (AAW) disproportionately. These patients are at increased risk for not only development of these cancers, but also experience disparities in survival, treatment outcomes, and modalities of treatment. Clinical Case: A 47-year-old premenopausal AAW with past medical history of recurrent desmoid sarcoma of the abdomen and ductal carcinoma in-situ (DCIS) of the left breast presented to oncology clinic with recurrent abdominal mass. The patient was originally diagnosed with DCIS in the left breast in 2018 and subsequently underwent left breast mastectomy with TRAM reconstruction and fat graft later that year. In 2020, the patient noticed a left lower abdominal growth that quickly enlarged and became painful. She underwent imaging without biopsy and was taken to surgery in April 2021 with tumor removal and mesh placement. Pathology showed desmoid fibromatosis infiltrating skeletal muscle and involving the inked resection margin of the specimen. Conservative re-excision and additional therapy was recommended but not done at the time. In 2022, the patient had resection of the area again with pathology of the incisional scar showing skin and deep soft tissue foci suspicious for recurrent desmoid fibromatosis extending to the inked deep margin. No mesh was placed, and the wound closed almost completely. The patient was not aware of positive margins at the time. In January 2023, patient again notice a new bump that was bothersome. Initial CT and MRI without finding of defined mass, but with right rectus thickening and enlarged right external iliac lymph node. Core biopsy in June 2023 confirmed recurrent desmoid fibromatosis. In April 2023, annual screening with mammogram was performed with a finding of 2.9 cm cluster of heterogenous calcification in the right breast. Diagnostic mammogram and ultrasound performed. Core needle biopsy was subsequently performed in May with pathology consistent with high grade DCIS with low ER and PR positivity. Lymph node biopsy was negative, but clinically positive. She is currently undergoing further genetic testing with surgical workup for mastectomy. Discussion and Conclusion: AAW diagnosed with DCIS have higher all-cause and disease specific mortality in comparison to white women (WW) diagnosed with DCIS. AAW are also at increased risk of aggressive secondary breast cancers in both the ipsilateral and contralateral breast in comparison to other races. In regards to tumor biology, WW have been shown to have higher ER and PR positivity in both primary and primary breast cancers than AAW. In many of these large-scale studies higher mortality, recurrence, and metastasis in AAW have been identified regardless of treatment modality. Research into differences in treatment between AAW and WW has shown that AAW, in contrast to our patient case, are more likely to undergo endocrine and radiation therapy rather than mastectomy. Although there does not seem to be an increased risk of desmoid fibromatosis in AAW when compared to WW, other soft-tissue tumors and malignancies do show a predilection for AAW. Incidence of sarcoma in black patients is higher than white patients, and black patients also have poorer survival outcomes. This case provides an example of the intersectionality of two cancer subtypes that impact black patients disproportionately. More evidence is required to unearth the reasons why these two cancer subtypes which are driven by similar processes impact AAW to a greater degree. Citation Format: Vinita Akula, Jessica Jones. Recurrent Desmoid Tumor and Ductal Carcinoma In Situ in an African-American Woman: A Case Report and Discussion on Disparities for These Two Cancer Subtypes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-21-01.

Volume-based 18F-FDG PET/CT predicts prognosis and outcome of active surveillance for intra-abdominal desmoid tumor.

Desmoid tumor (DT) is a rare monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Initial active surveillance is recommended by current guideline, and surgery is one of the main therapies for DT. Predicting the prognosis and outcome of active surveillance for intra-abdominal DT is pressing issue. The study included eighteen patients with intra-abdominal DT. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured. We analyzed their relationship with the outcome of active surveillance, as well as clinical, prognostic, and pathological data. The MTV and TLG of recurrent DT were significantly higher than those of non-recurrent DT (P < 0.001 and P = 0.00, respectively). The ROC curve suggested that the appropriate cutoff values for distinguishing recurrent DT from non-recurrent DT were 760.8 for MTV (sensitivity = 1, specificity = 0.857 and AUC = 0.929), and 1318.4 for TLG (sensitivity = 1, specificity = 0.786, and AUC = 0.911). The cutoff values of MTV and TLG significantly correlated with PFS using the Kaplan-Meier method (P = 0.002 and P = 0.007, respectively). MTV and TLG could distinguish DTs with subsequent progression from stable ones (P = 0.004 and P = 0.004, respectively). The ROC curve suggested that the appropriate cutoff values for distinguishing DTs with subsequent progression from stable ones were 197.1 for MTV (sensitivity = 0.9, specificity = 1, and AUC = 0.900), and 445.45 for TLG (sensitivity = 0.9, specificity = 1, and AUC = 0.900). Volume-based 18F-FDG-PET can predict prognosis of intra-abdominal DT. MTV and TLG can predict the outcome of active surveillance for intra-abdominal DT. MTV and TLG can potentially be predictors of surgical risk and difficulty.

Prognostic Factors for Local Recurrence after Cryoablation of Desmoid Tumors

PurposeTo determine the risk factors for local of adult patients treated for desmoid tumors by cryoablation. Materials and MethodsEighty-four patients treated for nonabdominopelvic desmoid tumors by cryoablation from July 2012 to July 2020 were included in a retrospective study. The population was composed of 64 women (76.19%) and 20 men (23.81%), aged from 16 to 75 years (median, 35 years ± 14.25). Each patient underwent preprocedural gadolinium-enhanced magnetic resonance imaging and was followed up to 36 months with the same technique. Clinical features, such as tumor size and previous treatment, epidemiological features, and the technical parameters of cryoablation, were studied. ResultsLocal relapse was found in 19 (22.62%) of 84 patients. The 12-, 24-, and 36-month progression-free survival rates were 89% (95% confidence interval [CI], 79–94), 74% (95% CI, 60–83), and 68% (95% CI, 53–79), respectively. In univariate analysis, significant prognostic factors associated with local recurrence were non–abdominal wall location (P = .042), debulking strategy (P = .0105), risk of visceral injury (P = .034) or peripheral nerve injury during cryoablation (P = .033), previous radiation therapy (P = .043), and treatment before 2016 (P = .008). In multivariate analysis, abdominal wall tumors displayed the best outcome, whereas the neck and trunk showed a high rate of recurrence (hazard ratio, 7.307 [95% CI, 1.396–38.261]). ConclusionsThe local recurrence of desmoid tumors after cryoablation depends on a number of prognostic factors, in particular, a non–abdominal wall location of the tumor and previous local treatment such as surgery or radiation therapy.

S2125 Short Time Recurrence of Retroperitoneal Desmoid Tumor in Patient With Familial Adenomatous Polyposis

Introduction: A Desmoid Tumor (DT) is a locally invasive, non-metastatic mesenchymal stem cell tumor that typically manifests as a soft tissue mass occurring in muscles, fasciae and aponeuroses. We present a case of a patient with recurrence of a retroperitoneal DT shortly after resection. Case Description/Methods: A 34-year-old male presented with abdominal pain found to have a large (11 × 14.4 * 14 cm) intrabdominal mass. IR transcatheter biopsy of the mass confirmed DT. He underwent bidirectional endoscopy and found to have more than hundred adenomatous colon polyps. Genetic testing confirmed APC mutation. Patient was diagnosed with DT associate with Familial Adenomatous Polyposis (FAP). He underwent radical resection of mesenteric mass and small bowel (20 cm of terminal ileum), omentectomy as well as total colectomy with ileorectal anastomosis. There was no evidence of lymphoid involvement. About 3 months later, he was re-admitted for increased abdominal girth with abdominal pain. MRI scans demonstrated a new, extensive, lobulated soft tissue mass occupying the entire abdominal cavity measuring 23.4 × 12.5 × 24.2 cm. Biopsy of the mass confirmed recurrent DT. Given the large size and proximity to the superior mesenteric artery, the mass was deemed to be unresectable. Patient was initially started on palliative systemic treatment with liposomal Doxorubicin. Due to lack of response, he was then switched to weekly methotrexate and Vinblastine (Figure). Discussion: DTs are rare neoplasms, making up only 0.03% of all neoplasms and 3% of soft tissue tumors. They typically include the abdominal wall, extremities, and mesentery. Although the etiology of DTs is not well known, there are several risk factors that are associated with their occurrence. Genetic syndromes such as FAP and Gardner syndrome have a well-known association with DTs. Other associations include antecedent trauma to the site of the lesion, pregnancy, and female sex. Numerous studies have been done assessing the efficacy of surgery, radiotherapy, and chemotherapy in managing DTs. However, none have shown conclusive benefit. The recurrence rate, particularly following surgical management, has been found to be as high as 77%. Given the lack of definitive management and high recurrence rates, treatment options should likely include combination of both surgical intervention and systemic treatment after discussing options and adverse effects of treatment with the patient.Figure 1.: A, Contrast enhanced CT axial through the lower abdomen demonstrating recurrence of large mass now occupying the majority of the abdominal cavity (black star); B, Spindle cell lesion, with fascicular and loose storiform growth patterns (H&E, 40×) prior to resection; C, Recurrent tumor with pathology demonstrating spindle cell lesion with more edema and/or myxoid stroma.

Surgical management of recurrent desmoid tumor in a young male

Desmoid tumors are rare, aggressive fibroblastic soft tissue tumors. We report a case of a 20-year-old male with recurrence of desmoid tumor of the left shoulder after initial complete resection 3 years prior. Pathology revealed fibromatosis desmoid type. After complete resection of tumor at 17-year-old, no symptoms were reported after 3 years of first resection, when he developed numbness and weakness of the left upper extremity. Magnetic resonance imaging demonstrated an enlarging arteriovenous malformation at the left shoulder with possible recurrence. Excision was performed, and after tissue examination evidence of recurrent fibromatosis desmoid type was found without arteriovenous malformation. Recurrence after complete resection could be as high as 70%. Early recurrence recognition is essential as tumor growth before the infiltration of the aggressive tumor makes the resection more difficult and increases surgical risk of complications.

High-Intensity Focused Ultrasound Ablation for Postoperative Recurrent Desmoid Tumors: Preliminary Results.

This study was aimed at evaluating the feasibility, safety and therapeutic effects of high-intensity focused ultrasound ablation (HIFUA) in the treatment of post-operative recurrent desmoid tumors. From September 2017 to May 2020, 42 consecutive patients with pathologically proven desmoid tumors treated with HIFUA for the first time were enrolled. These were divided into two groups: post-operative recurrent group (30 cases) and non-surgery group (12 cases). The basic characteristics, treatment parameters, ablation efficacy, tolerance and adverse events were recorded and compared between groups. The minimum distance between the tumor and skin surface in the post-operative recurrent group was significantly smaller than that in the non-surgery group (6.9 mm vs. 10.8 mm, p=0.011), but there was no significant difference in the other basic characteristics (p > 0.05). The average acoustic power and intensity of treatment in the post-operative recurrent group were significantly lower than those in the non-surgery group (p=0.006 and 0.036, respectively), but there was no significant difference in the remaining parameters or in ablation efficacy between groups (p > 0.05). HIFUA was successfully performed, and a large volume of coagulation necrosis was obtained from all patients without serious or life-threatening adverse events. Furthermore, there was no significant difference in the incidence of moderate adverse events and average length of stay between groups (p > 0.05). The average power and intensity of HIFUA treatment were adversely affected by surgical scar and tumor infiltration along the surgical path. However, HIFUA can still be used as an effective minimally invasive therapy for the local control of post-operative recurrent desmoid tumors.

The efficacy of low-power cumulative high-intensity focused ultrasound treatment for recurrent desmoid tumor.

BackgroundDesmoid tumors are rare neoplasms that are locally invasive. However, optimal treatment strategies for recurrent desmoid tumors remain controversial. High‐intensity focused ultrasound (HIFU) has been reported as a noninvasive modality for treating recurrent desmoid tumors. However, its efficacy against massive desmoid tumors or those with complex anatomies remains unclear.MethodsWe developed a new therapeutic strategy called low‐power cumulative HIFU and applied it to treat recurrent desmoid tumors.ResultsWe retrospectively collected data from 91 patients with recurrent desmoid tumors who underwent low‐power cumulative HIFU treatment after surgical treatment failure. The mean ablation proportion of the HIFU treatment was 69.5%, and the objective response rate was 47.3%. The 5‐year estimated progression‐free survival rate for these patients was 69.3%.ConclusionLow‐power cumulative HIFU treatment could achieve significant efficacy and long‐term control of recurrent desmoid tumors.

Multidisciplinary rescue of recurrent desmoid tumour. Performance in an advanced abdominal wall section

Revista monográfica de cirugía de la pared abdominal, digital y en lengua española. Artículos originales de investigación, editoriales, imágenes clínicas, cartas al director, reseñas de publicaciones, etc.

Recurrent Desmoid Tumor of the Abdominal Wall

Desmoid tumors or aggressive fibromatosis are monoclonal fibroblast proliferations. They are characterized by an invasive infiltrating capacity, a very high local recurrence rate but without metastatic potential. Imaging plays an essential role in diagnosis and therapeutic management is multidisciplinary. We report the case of a 60-year-old patient presenting with an abdominal mass of the left lateral wall gradually increasing in size and whose diagnosis of desmoid tumor of the abdominal wall was retained.

VP007 MULTIRECIDIVATED DESMOÍD TUMOR OF THE THORAX-ABDOMINAL WALL

Abstract Aim Treatment of recurrent desmoid tumors represents a real challenge for the surgeon. The purpose of the video is to show the treatment of a multirecidivated complex desmoid tumor that affects the lateral thoracoabdominal wall. Material and Methods 24-year-old woman with the diagnosis of recurrent desmoid tumor. She was operated in 2014 for a 10 cm desmoid tumor in the left chest wall with affected margins in the biopsy. In 2016 she underwent surgery for a 5 cm recurrence, which was excised en bloc along with the 6th, 7th, 8th and 9th rib arches. In 2018 she presented a recurrence in the scar treated by radiotherapy. She now presents a recurrence that in the CT scan is seen as an 8 cm tumor that affects the thoraco-abdominal wall. Results We perform a complete resection with free margins and “en bloc” resection of the 8th, 9th, 10th and 11th rib arches. We repair the defect using a reverse TAR and rebuild the wall with the Madrid APPROACH technique with BioA and polypropylene meshes. The patient was discharged 11 days after surgery without any complications. The pathological study showed an 8 cm desmoid tumor with free surgical margins. The patient a year after surgery remains disease free. Conclusions The resection of a desmoid tumor that affects the abdominal and/or thoracic wall, especially if it is recurrent, represents a challenge for the surgeon. Component separation techniques and Madrid APPROACH may be very useful to achieve an optimal repair.

Postoperative Adjuvant Radiotherapy Can Delay the Recurrence of Desmoid Tumors After R0 Resection in Certain Subgroups.

Background: When patients with desmoid tumors (DTs) present uncontrolled clinical symptoms, surgery is an effective treatment, but the high postoperative recurrence rate is a major problem. The significance of adjuvant radiotherapy has been debated for many years, and the significance of aggressive surgery has not been reported.Methods: Medical records for DT patients were collected. KM analysis and the Mann–Whitney U-test were performed to evaluate the role of radiotherapy and aggressive surgery in the entire cohort and different subgroups.Results: Of 385 DT patients, 267 patients with R0 resection were included in the final analysis. A total of 53 patients (19.85%) experienced recurrence. Although radiotherapy showed no significant effect on recurrence-free survival (RFS) or time to recurrence (TTR) in the entire cohort, radiotherapy delayed recurrence in the age ≤ 30 years old subgroup (TTR = 35 months with surgery plus radiotherapy, TTR = 11 months with surgery alone; p = 0.014) and the tumor diameter >5 cm subgroup (TTR = 26 months with surgery plus radiotherapy, TTR = 11 months with surgery alone; p = 0.02) among patients with a single tumor. Aggressive surgery improved RFS in the tumor diameter >5 cm subgroup (p = 0.049) but not the entire cohort.Conclusions: Although radiotherapy cannot improve RFS, it can delay recurrence in the age ≤ 30 years old subgroup and the tumor diameter >5 cm subgroup among patients with a single tumor. For patients with large invasive tumors and multiple involved sites, aggressive surgery could be selected to achieve complete tumor resection to improve RFS.

1523MO Initial active surveillance strategy for patients with peripheral sporadic desmoids: A multicentre phase II observational trial

Desmoid tumors (DT) are characterized by an unpredictable course. Most of the existing literature consists of retrospective studies. In a previous double-blind phase 3 trial comparing sorafenib and placebo, the 2-year Progression Free Survival (PFS) rate of the placebo group was 36% (Gounder NEJM 2018). However, assigned patients had already progressive or recurrent DT. The primary endpoint of this observational phase 2 study was to evaluate PFS and treatments at progression of newly diagnosed sporadic DT.

UN CAS DE TUMEUR DESMOÏDE (TD) DE LA PAROI ABDOMINALE PRIS EN CHARGE A LA CLINIQUE UNIVERSITAIRE DE CHIRURGIE VISCÉRALE DU CENTRE NATIONAL HOSPITALIER UNIVERSITAIRE (CNHU-HKM) DE COTONOU -BÉNIN.

Abstract Background Desmoid tumors are rare locally invasive tumors, but without metastatic potential. We report a case of recurrent locally advanced desmoid tumor of the anterior abdominal wall. We discuss the place of surgery and systemic treatments in the management of desmoid tumors. Report A 51-year-old woman presented at the Visceral Surgery Department of The National University Hospital (CNHUHKM) in January 2021 for a recurrent anterior abdominal wall tumor. The recurrence occurred 3 years after a first resection performed in 2008. The mass was centered on the umbilicus and was estimated 24 cm, ulcerated and hemorrhagic. She underwent a wide resection. Pathology report concluded to an ulcerated desmoid tumor. The postoperative course was uneventful. Eight months after resection, she showed no clinical signs of recurrence. Conclusion We presented a case of recurrent desmoid tumor of the abdominal wall. Although the indications for surgery have been restricted in recent years, it remains essential treatment for well selected patients. Key words: Desmoid tumor, abdominal wall, wide resection.

Prognostic significance of CTNNB1 mutation in recurrence of sporadic desmoid tumors.

Aim: Desmoid tumor (DT) is a rare, locally aggressive benign neoplasm withahigh recurrence rate. The majority of sporadic DTsare associated withmutations in CTNNB1, butwhether CTNNB1 mutations areassociated with the risk of DT recurrence remains unclear. The goal of this meta-analysis was to evaluate the association between CTNNB1 mutation and recurrence in surgically treated DT patients. Methods: PubMed, Embase and Cochrane library were systematically searched. The outcome of interest was the risk of recurrence. The number of patients with CTNNB1 mutation and the number of recurrences they developed were recorded and compared. The quality of these studies wasassessed using the Newcastle-Ottawa Quality Assessment Scale. Odds ratiosand variances were calculated and pooled. Results: A total of eight studies were identifiedincluding637 patients. S45F-mutated DTs were more likely to recur compared with wildtype, T41A and other mutated DTs. However, there were no statistically significant differences in the rate of recurrence between wildtype and T41A mutationor other mutation. Conclusions: Among CTNNB1 mutations, the mutationS45F is a high-risk factor for recurrence of DT and may be a predictive marker for the recurrence of sporadic DT.

A Case of Situs Inversus Totalis with Recurrence of Desmoid Tumor after Resection

A Case of Situs Inversus Totalis with Recurrence of Desmoid Tumor after Resection

S3605 A Case of Recurrent Desmoid Tumor Abscess in an Immunocompromised Patient

INTRODUCTION: Provider directed advice is important for patient acceptance in CRC screening. Recent evidence has suggested that physicians’ own screening practices might affect screening in their patients.1 METHODS: Medscape conducted a U.S. based web survey to determine if primary care physicians’ (PCPs) and Ob-Gyns’ (OB-GYNs) recommendations for CRC screening aligned with CRC screening choices that they would select for themselves. Email invitations were sent to 1500 members, and the survey remained open until at least 150 physicians were recruited; no reminder emails were sent. Data were collected anonymously; the study was exempt from IRB review. All participants were recruited and responded December 2 to December 5, 2019. Descriptive statistics were examined, and chi-square tests compared provider choices for patients for screening vs. choices for themselves. RESULTS: PCPs (n = 106) and OB-GYNs (n = 56) responded (survey response 11%) Mean age: 47 yrs; in practice 17 yrs. 62% group practice. 88% of physicians rated effectiveness of prevention as “very important” for why they recommend the tests they do for CRC screening (Table 1). However, when asked what their first choice for screening was, only 55% chose colonoscopy, with 33% choosing to discuss the pros and cons of all options and letting the patient decide (Table 2). Surprisingly, when this group was asked what their second choice was, only 13% said colonoscopy. When comparing self-choice vs. patient choice, there was a significant difference in the number who chose colonoscopy for themselves vs. their patients as the first choice both PCPs (x2 = 21.975(1), P < .001) but not OB/GYNs (x2 = 0.841(1), P = .359) (Table 3). CONCLUSION: Despite physician high ranking for CRC prevention, only 55% picked colonoscopy- the best CRC prevention test. Significant disparity is evident for PCP selection of self testing vs patient recommendation for CRC screening. Recognition of referring provider practice should open new understanding for educational messaging towards optimizing efforts for CRC prevention. The authors recognize that this survey may represent a convenience sample.Table 1.: Importance of the following for your typical recommendation to patients about CRC screeningTable 2.: Comparison of first /second choice% recommendations by providers to patients Note: Percentages in each column may not sum to 100% because of rounding a 2nd choice includes those who selected “discuss pros and cons” as a first choice; for that group (n = 44), order of choices: 46% FIT-fecal DNA test, 30% fecal immunochemical test, 16% colonoscopy, 7% guaiac based FOBT, 4% flexible sigmoidoscopy, 2% CT colonographyTable 3.: Comparison of first choice recommendations for patients vs providers themselvesa [a] Note: Percentages in each column may not sum to 100% because of rounding [a] excludes those who selected “I discuss pros and cons of tests and let patient decide” as the first choice

The Role of Visceral Transplantation for Neoplastic Disease

AbstractVisceral transplantation has been utilized as the most radical surgical treatment for neoplasms not amenable to conventional resection. The main indications for this procedure include mesenteric desmoid tumors threatening the root of mesentery and metastatic neuroendocrine neoplasms. Published case-series of visceral transplantation for such indications are reviewed in this article. Patients with desmoid tumors associated with familial adenomatous polyposis are transplanted with intestinal or multivisceral allografts. With surgical modification of technique, the native spleen is preserved while duodenopancreatic complex is removed to obviate the risk of malignant transformation of duodenal polyposis after transplantation. Preservation of spleen decreased incidence of post-transplant lymphoproliferative disorder, conferring therapeutic advantage. Patient survival is comparable to that of other indications, and desmoid tumor recurrence has been observed in the recipient tissue but not in the donor allograft. For visceral transplantation of metastatic neuroendocrine neoplasms, the majority of these patients have diffuse liver involvement, thus requiring full multivisceral transplantation. Post-transplant patient survival is acceptable with limited data available on recurrence. Autotransplantation following ex vivo tumor resection using visceral allografts has been also performed in a limited, select cohort of patients with various pathologies. Adenocarcinomas are associated with a prohibitive recurrence rate following the procedure, and its use for this indication is therefore not recommended. A national database of visceral transplantation undertaken for neoplastic disease should be developed to better understand predictors of outcomes and to help produce and standardize selection criteria.

SP4 Medicines optimisation in action: the development of a dosing schedule and an extemporaneous formulation of pazopanib to treat a child with a recurrent desmoid tumour of the head and neck

BackgroundInternational experts recommended pazopanib to treat a 9 year old boy with a recurrent desmoid tumour. The tumour had progressed, leading to blockage of the airway and dysphagia. The child had previously received three lines of intravenous chemotherapy as well as surgery and local radiotherapy. Treatment intent was to give an effective oral therapy with minimal side effects aiming to maintain a reasonable quality of life and prevent further life threatening respiratory compromise. As the child had an unsafe swallow, the drug would need to be given via a gastrostomy tube.Pharmacy InputA literature review was completed to establish the evidence to support the use and dose of pazopanib to treat desmoid type tumours in children.1 2 Attempts made to find a commercial supply of pazopanib liquid yielded no results. In the absence of any data or experience from other principal children’s cancer centres in the UK, first principles were used to review the physico-chemical properties of the molecule. Given the highly insoluble nature of pazopanib, an extemporaneous formulation for a pazopanib suspension was developed using Orasweet®, by adapting a formula suggested by the University of Oklahoma.3 A risk assessment for the preparation process was completed and a mini isolator was re-commissioned for this purpose following appropriate testing by Quality Control. The Department of Pharmacology at Newcastle University were contacted to establish if therapeutic drug level analysis might be possible. Local approval for pazopanib use was obtained from the Drug and Therapeutic Group and an IFR was submitted to NHS England.ChallengesIt was challenging to establish a dose regimen since the recommended paediatric dose from Phase I studies of pazopanib were dependent on the formulation used.1 4 Pharmacokinetic sampling was not possible as no assay had been developed in the UK. The lack of availability of any commercial or compassionate use liquid preparation meant that the only way of giving the drug to this child was to prepare an extemporaneous preparation, despite paucity of evidence to support the stability of the preparation. Funding was not approved by NHS England; local funding was agreed.Outcome and DiscussionThe child commenced treatment with the suspension in October 2018, administered via the gastrostomy tube. By July 2019 the patient had completed 10 cycles of therapy. Treatment was well tolerated. Minor side effects included abdominal and leg pain, vomiting, and a change in hair colour. The patient has had a good clinical response and a recent scan has shown substantial improvements in morphological appearance and size of the tumour.These results indicate that a locally prepared extemporaneous oral chemotherapy suspension can be successfully used to deliver treatment for a rare type of children’s cancer. Pharmacy colleagues from across the department collaborated to facilitate this novel treatment option.ReferencesGlade Bender J, Lee A, Reid J, et al. Phase I pharmacokinetic and pharmacodynamic study of pazopanib in children with soft tissue sarcoma and other refractory solid tumors: a children’s oncology group phase I consortium report. JCO 2011;31:3034–3043.Agresta L, Lee H, Turpin B, et al. Pazopanib therapy for desmoid tumors in adolescent and young adult patients. Pediatr Blood Cancer 2018;65:e26968.Allen L Jr. Pazopanib 50 mg/ml oral suspension. US Pharm 2015;40:61–62.Heath E, Forman K, Malburg L, et al. A phase I pharmacokinetic and safety evaluation of oral pazopanib dosing administered as crushed tablet or oral suspension in patients with advanced solid tumors. Invest New Drugs 2012;30:1566–1574.

Desmoid Type Fibromatosis of the Breast: Ten-Year Institutional Results of Imaging, Histopathology, and Surgery

Background: Desmoid type fibromatoses has proven to be a diagnostic and therapeutic challenge, as they often appear primarily as a carcinoma of the breast with a high recurrence risk. Patients: A digital archive search was performed for the period from 2009 to the end of 2018. Inclusion criteria consisted of histological examination of at least the surgical specimen in the reference pathology department and at least a second opinion diagnosis in the reference radiology department. Results: A total of 14 women and 1 man underwent surgery on desmoid type fibromatosisof the breast. The average patient age was 49 years (range: 22–72 years). The mean tumor size was 2.2 cm (range: 0.8–4.2 cm). The tumor was detectable in mammography in 12 out of 13 patients and in all 15 patients in sonography. MRI was performed preoperatively in 6 patients; in all of the patients, the tumor was visualized with inhomogeneous contrast enhancement. In the imaging procedures, all desmoid type fibromatoses were classified as suspicious. Performing the core biopsy, preoperative histology confirmed desmoid fibromatosis in 12 out of 15 patients. Nuclear stain for ß-catenin was positive in 7 out of 10 patients.Negative staining was found for AE1/A3 in 10 out of 10 and CD34 in 12 out of 12 patients. In all of the patients, a single-stage operation without the detection of border-forming tumor margins was performed. The follow-up interval ranged from 16 to 96 months (mean: 44.86 months, median: 43 months). In this follow-up period, no patient was diagnosed with desmoid tumor recurrence. Conclusion: In imaging, desmoid type fibromatosis of the breast has typical malignancy-related criteria. Extensive preoperative diagnostics enable the planning of complete primary excision of the lesion and reduce the recurrence risk.