TNM staging
The details of the mammary and superficial neoplasms studied in three groups and the TNM staging are depicted in Fig 1, Fig 2 and Table 1. Animals of group I had normal sentinel lymph nodes with very less reactive changes and group II and III animals had reactive to metastatic changes in the lymph node. The physical examination findings of lymph nodes were in accordance with
Tuohy et al., (2009) who reported the importance of routine sentinel lymph node evaluation as the most important step in TNM staging and clinical assessment aiding in surgical decision making in veterinary oncology. In the present study, early pulmonary metastasis signs were characterized based on the size in ascending order form by fine dots of miliary nodules, pulmonary micronodules, pulmonary nodule, pulmonary mass, multiple solid nodules, single solid mass, cavitary nodules and single cavity mass. Similar classifications were followed by
Spasov et al., (2018) and
Weerakkody (2019). The animals of group II had early metastatic changes and were subjected to neoadjuvant chemotherapy. This was in accordance with
Gustafson and Bailey (2019) who recommended neoadjuvant chemotherapy for down staging cancer. The neoadjuvant chemotherapy was also intended for preventing the tumour spread and defining the surgical margin for resection. Similar recommendations were given by
Chun et al., (2007). The animals selected in the group III had advanced pulmonary metastasis and warranted adjuvant chemotherapy after marginal excision of the neoplasms. Similar recommendations were given by
Farese et al., (2019).
Histopathological findings
The details of histopathological analysis and grading of neoplasm are depicted in Table 1. In group I animals, TNM staging (T
A N
0-1 M
0) were correlated with benign neoplasms like adenoma, lipoma and benign mixed tumour. Group II (T
A N
0-1 M
0-1) and group III animals (T
A N
0-1 M
1) were identified as having neoplasms with aggressive histopathological features of inflammatory carcinoma, intraductal papillary carcinoma, comedocarcinoma, ductal carcinoma, malignant mixed tumour neoplasms, anaplastic carcinoma, osteogenic melanoma, carcinosarcoma, synoviosarcoma and fibrosarcoma.
Response evaluation
Response Evaluation Criteria In Solid Tumours (RECIST) and Modified Karnofsky performance status used to study response evaluation assessment in third and sixth month are enlisted in Table 1. All the cases of group I showed RECIST parameter of CR (complete response) characterized by the disappearance of all target lesions and 100 per cent resolution of neoplasm as observed in the third and sixth-month review with Modified Karnofsky performance status scale 0. Recurrence with advanced pulmonary metastasis despite multimodal therapy of adjuvant chemotherapy was noticed in high grade malignant neoplasms. In Group II and III malignant neoplasms showed invaluable response (IR) to treatment and animals with advanced pulmonary metastasis died on eighth and tenth month respectively. Progressive disease with increase in pulmonary metastasis were reported in invasive carcinoma mammary gland, Anaplastic carcinoma and Trichoblastic carcinoma among Group III animals. These observations were found in accordance with
Parachini et al., 2019 who reported that pulmonary metastasis of cutaneous and subcutaneous malignant neoplasms could be considered as a terminal event in dogs. The Kaplan Meier survival curve and log-rank test were used to interpret the results and assess the QOL of the patients after the treatment. The details are depicted in Fig 3. The log-rank test tested the null hypothesis that there existed non significant difference in the overall survival distribution between the groups. In the present study c2 value was 9.061, p<0.05, therefore, the null hypothesis was rejected indicating that there existed a significant difference between survival distributions for the three groups. The severity of the cases on presentation and the malignancy were more in group III and was correlated with a lower mean survival time of 9.38±0.92 months in group III (T
AN
1M
1), compared to 12.194±0.65 months in group II (T
A N
1 M
0-1) and 17.12±0.82 months in Group-I. Previous studies by
Karayannopoulou et al., (2001) and
Yamagami et al., (1996) also reported lower survival rates in dogs with regional lymph node metastasis than those without lymph node involvement and worst prognosis with distant metastasis. Neoadjuvant chemotherapy or primary chemotherapy selected based on the TNM staging served to downstage a chemo sensitive neoplasm (cytoreduction) before performing a definitive surgical therapy. Similar findings were reported by
(Chun et al., 2007), Gustafson and Bailey (2019). The adjuvant chemotherapy acted as an adjunct treatment modality in case of extensive neoplasms with stages T
A N
1 M
0-1 delaying the recurrence after incomplete surgical excision and also to slow down the distant metastasis.
Brunnberg et al., (2016) also reported similar findings. Recurrence with advanced pulmonary metastasis despite multimodal therapy of adjuvant chemotherapy was noticed in animals with invasive ductal carcinoma, soft tissue sarcoma (STS) and other malignant superficial neoplasms like osteogenic melanoma, carcinosarcoma, synoviosarcoma and fibro sarcoma. These findings were in accordance with
Tran et al., (2016) and
Bray, (2016).
