Concurrent Imatinib and Radiation Therapy for Unresectable and Symptomatic Desmoid Tumors

Abstract

Desmoid tumors are locally aggressive fibroproliferative neoplasms that can lead to pain and dysfunction due to compression of nerves and surrounding structures. Desmoid tumors often progress through medical therapy, and there is frequently a delay of multiple months before radiation can provide symptomatic relief. To achieve more rapid symptomatic relief and tumor regression for unresectable desmoid tumors causing significant morbidity such as brachial plexus impingement with loss of extremity function, we have selectively utilized a combination of imatinib and radiation therapy. Here, we retrospectively review four patients treated with concurrent imatinib and radiation therapy. The treatment was typically tolerated with minimal toxicity though one patient developed avascular necrosis of the irradiated humeral head possibly related to the combined treatment. All the patients treated have had a partial response or stable disease on imaging. Improvement of symptoms was observed in all the treated patients with a median time to relief of 2.5 months after starting radiation therapy. Concurrent radiation and imatinib may represent a viable treatment option for unresectable and symptomatic desmoid tumors where rapid relief is needed to prevent permanent loss of function.

AXL Mediates Cetuximab and Radiation Resistance Through Tyrosine 821 and the c-ABL Kinase Pathway in Head and Neck Cancer

“…report that c-ABL may be a critical signaling axis leading to resistance. Supporting this finding are several studies performed by other groups showing imatinib combined with radiation treatment was very effective at delaying tumor and cell growth in different types of cancer including desmoid tumors, glioblastoma, breast cancer, and bladder cancer through various mechanisms (38)(39)(40)(41)(42)(43)(44). Our study corroborates these findings by showing that the combination of c-ABL inhibition, via genetic or pharmacologic approaches, was able to overcome resistance to radiation in HNSCC PDX model systems.…”

Management of Patients with Newly Diagnosed Desmoid Tumors in a First-Line Setting

“…These findings are interesting since among all systemic medical therapies, TKIs were the only ones to be non-inferior to surgery plus adjuvant radiotherapy in terms of PFS. This might be secondary to the fact that more than half of patients who received TKIs were treated with imatinib plus adjuvant radiotherapy, an approach that we have been implementing to achieve better local control and faster symptom relief for patients who have unresectable tumors due to the involvement of neurovascular structures [ 25 ]. Similar results were observed in terms of TTNT, where TKIs were inferior only to surgery plus radiotherapy, but were the only treatment modality to achieve similar TTNT compared to surgery alone.…”

Abscopal Effect of Radiotherapy in Imatinib-resistant Dermatofibrosarcoma Protuberans

“…There are currently few reported cases showing the clinical benefits of concurrent IM and radiotherapy for which lower radiation doses have been used to achieve desirable outcomes [ 7 ]. In a preclinical study of muscle-invasive bladder cancer, IM acted as a radiosensitizer by targeting homologous recombination [ 20 ].…”

“…Immune-mediated effects have been noticed with therapies such as imatinib [ 6 ]. Concurrent imatinib with radiotherapy has been used to achieve a desirable outcome at a lower radiation dose in desmoid tumors [ 7 ], but its systemic anti-tumor effect is yet to be observed. Despite the advantages the abscopal effect may have on overall survival and disease-free progression, its relevance in current radiation treatment protocols remains uncertain because of the paucity of research in that area [ 3 ].…”