Response to sunitinib in combination with proton beam radiation in a patient with chondrosarcoma: a case report

Dallas, Jennifer; Imanirad, Iman; Rajani, Rajiv; Dagan, Roi; Subbiah, Sukanthini; Gaa, R; Dwarica, Wayne A; Ivey, Alison Marguerite; Zlotecki, Robert A.; Malyapa, Robert S.; Indelicato, Daniel J.; Scarborough, Mark T.; Reith, John D.; Gibbs, Charles P.; Dang, Long H.

doi:10.1186/1752-1947-6-41

Cited by 12 publications

(11 citation statements)

References 21 publications

(18 reference statements)

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“… 3 A case report describing the successful treatment of a patient with chondrosarcoma by combining P radiotherapy with sunitinib, an inhibitor of VEGFRs and platelet-derived growth factor receptor, underlines the effectiveness of such approach. 36 …”

Section: Discussionmentioning

confidence: 99%

Effects of proton versus photon irradiation on (lymph)angiogenic, inflammatory, proliferative and anti-tumor immune responses in head and neck squamous cell carcinoma

et al. 2017

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The proximity of organs at risk makes the treatment of head and neck squamous cell carcinoma (HNSCC) challenging by standard radiotherapy. The higher precision in tumor targeting of proton (P) therapy could promote it as the treatment of choice for HNSCC. Besides the physical advantage in dose deposition, few is known about the biological impact of P versus photons (X) in this setting. To investigate the comparative biological effects of P versus X radiation in HNSCC cells, we assessed the relative biological effectiveness (RBE), viability, proliferation and mRNA levels for genes involved in (lymph)angiogenesis, inflammation, proliferation and anti-tumor immunity. These parameters, particularly VEGF-C protein levels and regulations, were documented in freshly irradiated and/or long-term surviving cells receiving low/high-dose, single (SI)/multiple (MI) irradiations with P/X. The RBE was found to be 1.1 Key (lymph)angiogenesis and inflammation genes were downregulated (except for vegf-c) after P and upregulated after X irradiation in MI surviving cells, demonstrating a more favorable profile after P irradiation. Both irradiation types stimulated vegf-c promoter activity in a NF-κB-dependent transcriptional regulation manner, but at a lesser extent after P, as compared to X irradiation, which correlated with mRNA and protein levels. The cells surviving to MI by P or X generated tumors with higher volume, anarchic architecture and increased density of blood vessels. Increased lymphangiogenesis and a transcriptomic analysis in favor of a more aggressive phenotype were observed in tumors generated with X-irradiated cells. Increased detection of lymphatic vessels in relapsed tumors from patients receiving X radiotherapy was consistent with these findings. This study provides new data about the biological advantage of P, as compared to X irradiation. In addition to its physical advantage in dose deposition, P irradiation may help to improve treatment approaches for HNSCC.

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Section: Discussionmentioning

confidence: 99%

Effects of proton versus photon irradiation on (lymph)angiogenic, inflammatory, proliferative and anti-tumor immune responses in head and neck squamous cell carcinoma

et al. 2017

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“…Combining sunitinib with high dose radiation therapy resulted in fatal toxicities, though each treatment was well tolerated alone, thus limiting the feasibility of this combination (D’Amico et al, 2012). Unfortunately, success with the combination of sunitinib and radiation has been on a case by case basis, with no clinical series to date assessing the potential synergy of this combination (Dallas et al, 2012; Venton et al, 2012). …”

Section: Different Strategies To Down-regulate Mdsc Number and Functionmentioning

confidence: 99%

Clinical Perspectives on Targeting of Myeloid Derived Suppressor Cells in the Treatment of Cancer

2013

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Tumors escape immune recognition by several mechanisms, and induction of myeloid derived suppressor cells (MDSC) is thought to play a major role in tumor mediated immune evasion. MDSC arise from myeloid progenitor cells that do not differentiate into mature dendritic cells, granulocytes, or macrophages, and are characterized by the ability to suppress T cell and natural killer cell function. They are increased in patients with cancer including renal cell carcinoma (RCC), and their levels have been shown to correlate with prognosis and overall survival. Multiple methods of inhibiting MDSCs are currently under investigation. These can broadly be categorized into methods that (a) promote differentiation of MDSC into mature, non-suppressive cells (all trans retinoic acid, vitamin D), (b) decrease MDSC levels (sunitinib, gemcitabine, 5-FU, CDDO-Me), or (c) functionally inhibit MDSC (PDE-5 inhibitors, cyclooxygenase 2 inhibitors). Recently, several pre-clinical tumor models of combination therapy involving sunitinib plus vaccines and/or adoptive therapy have shown promise in MDSC inhibition and improved outcomes in the tumor bearing host. Current clinical trials are underway in RCC patients to assess not only the impact on clinical outcome, but how this combination can enhance anti-tumor immunity and reduce immune suppression. Decreasing immune suppression by MDSC in the cancer host may improve outcomes and prolong survival in this patient population.

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“…Unfortunately these novel drugs are only accessible in clinical studies, and only for patients with unresecteble or metastatic tumors 42 . Chemotherapy is not effective in chondrosarcoma, however new chemotherapeutic agents like pemetrexed or sumantinib are currently evaluated 43,44 .…”

Section: Limitation Of the Non-surgical Therapymentioning

confidence: 99%

Surgical treatment of primary malignant tumors of the sacrum

Varga¹,

Szövérfi²,

Lazáry³

2014

Neurological Research

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Response to sunitinib in combination with proton beam radiation in a patient with chondrosarcoma: a case report

Cited by 12 publications

References 21 publications

Effects of proton versus photon irradiation on (lymph)angiogenic, inflammatory, proliferative and anti-tumor immune responses in head and neck squamous cell carcinoma

Effects of proton versus photon irradiation on (lymph)angiogenic, inflammatory, proliferative and anti-tumor immune responses in head and neck squamous cell carcinoma

Clinical Perspectives on Targeting of Myeloid Derived Suppressor Cells in the Treatment of Cancer

Surgical treatment of primary malignant tumors of the sacrum

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