A real-world study on the clinicopathological profile, treatment outcomes and health-related quality of life, anxiety and depression among patients with desmoid tumor at two tertiary care centers in India

Background: The medical management of DT comprises tyrosine kinase inhibitors (TKIs), hormonal agents, anti-inflammatory drugs with the recently approved gamma secretase inhibitor nirogacestat being the current standard of care. Real-world data on evolving treatment landscapes of DT remains scarce.

Methods: This is a retrospective study of patients with DT registered between 1995 and 2020 at All India Institute of Medical Sciences, New Delhi and Tata Medical Center, Kolkata. Baseline characteristics were analyzed in form of median values and interquartile range. Categorical and continuous variables were compared by chi square and independent samples T- tests respectively. Anxiety, depression and QoL were prospectively measured among 30 patients using Hospital Anxiety and Depression (HADS) and Functional Assessment of Cancer Therapy-General (FACT-G) scales respectively between 2022 to 2023.

Results: 200 patients were included with a male-predominant (n=111, 55.5%) population and median age 26.5 (2.5-75) years. Extremity (n=100, 50%) and abdomen (n=65, 32.5%) were commonest primary sites and median of 2 (1-4) lines of treatment were received. First-line included surgery (n=116, 58%), systemic therapy (n=67, 33.5%), radiotherapy (10, n=5%) and active surveillance (n=7, 3.5%). First-line systemic agents included tamoxifen (n=55, 27.5%), imatinib (n=7, 3.5%), sorafenib (n=1, 0.5%) and chemotherapy (n=4, 2%). 2019 onward, 3% and 63% underwent active surveillance and surgery respectively. Best radiological response obtained with tamoxifen was stable disease (SD) (n=76, 59%) and partial response (PR) (n=31, 24.2%). Best radiological response obtained with sorafenib was PR (n=17, 60.7%) and SD (n=9, 32.1%). Thirty patients underwent HADS and FACT-G scale assessment. Mean HADS-Anxiety subscale score was 3.6 (+/-3.9 SD) and HADS-Depression sub-scale score was 2.6 (+/-3.5 SD) with clinically significant anxiety and depression in 2 (6.7%) patients each. The overall mean FACT-G score was 87.5 (+/-12.6 SD) and lower mean physical well-being (p=0.006) and emotional well-being (0.017) scores were significantly associated with higher HADS-anxiety (>/=8) scores.

Conclusions: Assessment of anxiety, depression and QoL are paramount to gauge the psychological impact of DT. This study gives an overview of clinical and management profile of patients with DT in India, with limitations of selection bias, heterogeneous population and small sample size for QoL assessment.

Background As desmoid-type fibromatosis (DF) exhibits a high recurrence rate after surgery, initial active surveillance followed by medical therapy is the mainstay of the treatment. However, there are few effective drugs with acceptable side effects. Methodology Among drugs that have been used for a long period and possess a known safety profile, auranofin was observed to be effective in suppressing DF using the drug repositioning method in our laboratory. This clinical study has been designed to examine the efficacy and safety of auranofin, an approved anti-rheumatic drug, in patients with progressive DF. Results This study is conducted as a single-center, single-arm, open-label study. Auranofin 3 mg tablets will be administered twice daily to DF patients with progressive disease. The primary endpoint is progression-free survival at 26 weeks after starting treatment. Secondary endpoints include response rate, T2-weighted MRI evaluation, pain intensity, quality of life (QOL), and safety assessment. Conclusions This is the first clinical trial of auranofin in patients with aggressive DF. The study will allow an in-depth understanding of the efficacy of auranofin for response rate as well as for changes in MRI findings, pain, and QOL in patients with aggressive DF.

Purpose: To determine the efficacy and safety of cryoablation in pediatric and young adult patients with desmoid tumors (DTs) retrospectively over a 10-year period.

Materials and methods: Twenty-one patients (age 2-22 years; median 14 years), with 21 desmoid tumors, underwent a total of 34 percutaneous cryoablation procedures between August 2013 and August 2023. All patients, excluding two, had surgical resection, chemotherapy, or a combination of these therapies with failed or suboptimal response. Clinical and imaging outcomes were analyzed for technical success, change in tumor volume, and recurrence of tumor, symptom improvement or recurrence, and procedure-related complications.

Results: All procedures were technically successful. The median follow-up duration was 9 months (range, 3-32 months); total symptomatic improvement was achieved in 90% (19/21) patients, noticeable pain relief was seen in 100% (18/18) and 90% (9/10) patients had improved range of motion (ROM), discomfort resolved in 66.7% (2/3) patients. Of the treated tumors, 43% (9/21) showed greater than 75% tumor volume reduction of which 44% (4/9) had no evidence of viable residual tumor at follow-up, and 33% (7/21) had 50-75% volume reduction and 14% (3/21) had greater than 40-50% tumor volume reduction. According to modified response evaluation criteria in solid tumors (mRECIST), 71%( 15/21) had partial response (PR), 19% (4/21) had complete response (CR), and 10% (2/21) had stable disease. Four (12%) treatments were associated with minor complications, which self-resolved.

Conclusion: In this, predominantly pediatric patient cohort, cryoablation was effective and safe for the local control of extra-abdominal desmoid tumors in short-term follow-up.

Importance: Improved prognostic tools are needed for patients with locally recurrent extremity or truncal soft tissue sarcoma (STS).

Objective: To examine the association between average local recurrence (LR) growth rate and outcomes following resection of locally recurrent extremity or truncal STS.

Design, setting, and participants: This retrospective cohort study used a prospectively maintained database from a single high-volume tertiary sarcoma referral center in the US to identify patients 16 years of age or older who underwent repeat resection of a locally recurrent extremity or truncal STS between July 1, 1982, and December 31, 2021. Patients with atypical lipomatous tumors, desmoid tumors, dermatofibrosarcoma protuberans, angiosarcomas, and prior or synchronous distant recurrence were excluded. Data were analyzed from November 1, 2022, to June 17, 2024.

Exposure: Average LR growth rate, defined as the sum of recurrent tumor maximal diameters divided by the disease-free interval after index operation.

Main outcomes and measures: The primary outcomes were cumulative incidences of disease-specific death (DSD), with death from other causes as a competing risk, and second LR, with death from any cause as a competing risk.

Results: The study cohort included 253 patients (median [IQR] age, 64 [51-73] years; 140 [55.3%] male). The 5-year cumulative incidence of DSD after repeat resection was 29%. Multivariable analysis indicated that LR growth rate (hazard ratio [HR], 1.12 [95% CI, 1.08-1.18]; P < .001), younger age (HR, 0.98 [95% CI, 0.97-0.99]; P = .002), R1 or R2 margins (HR, 1.71 [95% CI, 1.03-2.84]; P = .04), high LR grade (HR, 2.90 [95% CI, 1.17-7.20]; P = .02), and multifocality (HR, 2.92 [95% CI, 1.70-5.00]; P < .001) were independently associated with higher incidence of DSD. Using the minimum P value method, the optimal cutoff for growth rate was found to be 0.68 cm/mo. Patients with values above this cutoff had higher 5-year incidences of DSD following repeat resection (63% vs 19%; permutation test P < .001) and higher amputation rates (19% vs 7%; P = .008). Only R1 margins were independently associated with higher incidence of second LR (HR, 1.81 [95% CI, 1.19-2.78]; P = .006). Conclusions and relevance: In this cohort study of patients undergoing resection of a locally recurrent extremity or truncal STS, LR growth rate was independently associated with DSD. These findings suggest that patients with growth rates higher than 0.68 cm/mo who undergo LR resection may have high disease-specific mortality and amputation rates and should be considered for perioperative systemic therapy.

Myxomas, when they manifest in the paranasal sinuses and/or maxillae of infants, are classified as sinonasal myxomas (SNMs). We present a case of SNM in the maxilla of a 15-month-old infant. Following the initial surgical intervention, the patient unfortunately experienced a recurrence of the condition. However, a subsequent surgery employing marginal excision was performed, and since then, no further recurrence has been reported. SNM exhibits consistent clinical features and histological characteristics that are distinct from those of odontogenic myxomas. Furthermore, in this case, immunohistochemical staining was positive for β-catenin, whereas odontogenic myxomas are generally negative for β-catenin staining. Another study reported that SNMs share genetic mutations with desmoid tumors, which are not observed in odontogenic myxomas. This suggests that this entity is distinct from odontogenic myxomas, leading us to propose that it may indeed represent a separate disease entity. This fact may lead to the reclassification of the disease and, ultimately, to changes in treatment strategies.

Soft tissue sarcomas (STS) have long been a formidable challenge in oncology, partly because of their rarity and diversity, which complicates large-scale studies and slows the advent of new treatments. Traditionally anchored by anthracycline-based chemotherapy, the landscape of STS treatment hasn’t shifted dramatically in the past twenty years. However, recent strides in research are starting to paint a more hopeful picture. Leveraging advanced molecular profiling, researchers are now tailoring treatments to the unique genetic makeup of tumors, with targeted therapies showing promise. Innovations such as NTRK inhibitors for NTRK-rearranged sarcomas and gamma-secretase inhibitors for desmoid tumors are changing clinical practices. The rise of immunotherapy, including novel agents like LAG-3 inhibitors and bifunctional proteins that target both TGF-β and PD-L1, offers new avenues for treatment, particularly when combined with traditional therapies like chemotherapy. Meanwhile, the approval of epigenetic treatments for specific sarcoma subtypes heralds a new wave of strategy based on histological specificity, which could lead to more personalized and effective care. While challenges remain, the field of STS treatment is evolving, driven by a deeper understanding of the disease’s biological underpinnings and a commitment to innovative research approaches.