Clinical outcome in dogs with cutaneous mast cell tumors treated with neoadjuvant prednisolone and surgical excision

Abstract

肥大細胞瘤為犬最常見的皮膚型腫瘤，具有多變的生物行為。Prednisolone在臨床上常被用作前導型藥物來治療肥大細胞瘤，且報告中指出其並不會造成投予後相關的併發症發生。本實驗的目的在於以口服prednisolone，40 mg/m2，一天一次，作為前導型藥物治療犬之肥大細胞瘤，隨後分為外科組與無外科組，並評估病患之局部腫瘤復發之情形、無復發間期及總存活時間。而犬肥大細胞瘤的組織分級則採用修飾型二分類組織分級系統來進行。本實驗將57隻已被診斷為肥大細胞瘤的患犬分為二組，分別是：（1）NA組，共29隻患犬，為無外科組；（2）NAS組，共28隻患犬，為外科組。在NAS組中之29隻患犬，若以三個月作為評估復發之期限，則有25隻（87.2%）於三個月內沒有出現腫瘤復發的情形；其無復發間期的中位數為39天，範圍從30天到71天。罹患低分級肥大細胞瘤之患犬，具有較長的無復發間期，但其無復發間期在罹患不同分級之肥大細胞瘤的患犬間（P = 0.294）並不具有顯著差異。另外，在NAS組中，於組織學上低分級的患犬其總存活時間中位數為225天（範圍從20天至1152天）；而組織學上高分級的患犬，其總存活時間之中位數為180.5天（範圍從19天至850天）；然而，兩者並不具有顯著差異（P = 0.114）。在NAS組之患犬，有九隻犬的肥大細胞瘤最大直徑超過5 cm或為高分級者，總存活時間中位數為355天，範圍從76到850天，平均總存活時間為293天。在NA組之患犬，總存活時間中位數為48天，範圍從6到622天。在NA組之患犬，有五隻犬的肥大細胞瘤最大直徑超過5 cm或為高分級者，總存活時間中位數為84天，範圍從33到183天，平均總存活時間為106天。對於給予prednisolone 進行治療者，結果顯示，61%之肥大細胞瘤對於給予prednisolone治療是有反應的，其中完全消退有一個，佔2.4％，而部分消退有24個，佔58.5%，平均消退百分比為75.4%。對於在組織學上屬於低分級或高分級的肥大細胞瘤，其對prednisolone治療的反應並不具顯著差異（P=0.805），其中達完全消退有一個，為高分級肥大細胞瘤；而達部分消退者，有16個為低分級、8個為高分級，而在低分級肥大細胞瘤之平均消退百分比為80.8%，高分級者則為54.2%。而腫瘤大小達到最大消退之中位時間為21天。總結以上結果，prednisolone可造成多數的（超過一半以上的）肥大細胞瘤顯著消退，即便是在高分級的肥大細胞瘤同樣可達到顯著消退。另外，罹患肥大細胞瘤之患犬，尤其是其肥大細胞瘤最大直徑大於5 cm或為高分級者，也許可以選擇先給予三週口服prednisolone前導型治療後，再進行手術切除團塊的方式來治療。

Mast cell tumors (MCTs) are most common cutaneous tumors in dogs, which have various biological behaviors. Prednisolone, as a neoadjuvant, is widely used in the treatment of MCTs, and without reported postoperative complications. The aims of this study were to evaluate the relapse free interval (RFI), overall survival time (OST), and locoregional recurrence of dogs with MCTs after receiving oral prednisolone at a dose of 40 mg/m2 body surface area (BSA) once daily and assigning to follow with or without surgery. The MCTs were graded by modified 2-tier histologic grading system. Fifty-seven dogs diagnosed with MCTs were assigned to two groups: (1) NA group, 29 dogs, not followed by surgery; (2) NAS group, 28 dogs, followed by surgical removal. When evaluated not exceed three months, 25 of 29 (87.2%) dogs in NAS group had no recurrence of their tumors within 3 months; the median RFI was 39 days, ranging from 30 to 71 days. Of NAS group, dogs with low grade MCTs had longer RFI; however, there were no significant difference (P = 0.294). The median OSTs of dogs in NAS group with low grade and high grade MCTs were 225 days (ranging from 20 to 1152 days) and 181 days (ranging from 19 to 850 days), respectively, and without significant difference (P = 0.114). Night dogs of NAS group and with the maximum diameter of the mass over 5 cm or with high grade MCTs, the median OST was 355 days, ranging from 76 to 850 days, and the mean OST was 293 days. Dogs in NA group, the median OST was 48 days, ranging from 6 to 622 days. Five dogs of NA group and with the maximum diameter of the mass over 5 cm or with high grade MCTs, the median OST was 84 days, ranging from 33 to 183 days, and the mean OST was 106 days. The overall response rate of prednisolone was 61% and mean response was 75.4%. One mass had complete response [CR] (2.4%) and 24 masses had partial response [PR](58.5%). There was no significant difference comparing low grade with high grade MCTs (P=0.805). There was only one high grade MCT had CR. In addition, there were 16 low grade MCTs and 8 high grade MCTs had PR. In low grade MCTs, the mean regression percentage was 80.8%; in the other hand, it was 54.2% in high grade MCTs. The median time-span for reaching maximal tumor regression was 21 days. In conclusion, prednisolone can induce dramatic MCTs reduction even with high grade tumors. Based on the observations from this study, treatment of neoadjuvant prednisolone for 3 weeks followed by surgical removal might be recommended for patients with MCTs, especially with the maximum diameter of the mass over 5 cm or high grade MCTs.