e16507 Background: Oesophageal cancer is the twelfth most common cancer worldwide and seventh leading cause of cancer related death. Neoadjuvant treatment in addition to surgery has shown improved overall survival compared to surgery alone in resectable oesophageal cancer. We aimed to analyse the survival outcome among locally advanced oesophageal carcinoma patients in neoadjuvant setting. Methods: We analysed 37 patients with locally advanced carcinoma of oesophagus from 2015 to 2019 who underwent neoadjuvant chemoradiotherapy followed by surgical excision of tumour. Descriptive analysis was used for demographic data. overall survival and disease free survival was analysed using Kaplan-Meier survival analysis. Results: Our study includes 20 males (54%) and 17 females (45%). Over all consumption of Tobacco and alcohol consumption was found to be 64% and 18% respectively. The most common tumour site in this study was middle oesophagus (56%) followed by lower (37%) and upper (5%). Histopathologically, moderately differentiated squamous cell carcinoma constituted the highest (62%), followed by well differentiated squamous cell carcinoma (21%) and poorly differentiated carcinoma (16%). The pathological stage post chemoradiotherapy was 80%, 50% and 57% for stage I, II and III respectively. Median over all survival is 60 months and no statistical difference in stage I and stage II. Median over all survival for poorly differentiated squamous cell carcinoma is 16 months and lower one third of squamous cell carcinoma is 37 months. Complete pathological response is 42 %. Conclusions: Our study concluded that patients with tobacco and alcohol consumption have poorer survival. Prognosis was worst for patients with lower end oesophagus and poorly differentiated type. Disease free survival was better for patients who achieved complete pathological response when compared to partial responders.
e14603 Background: Immune check point inhibitors clearly play a part in malignancies with elevated PDL1 expression, high TMB or unstable MSI. There is no information on PDL1 negative, low TMB/MSI stable metastatic solid tumours, however several treatment trials advise using immune check point inhibitors regardless of tissue agnostic indicators. Detailed subset analysis was not performed, though. This study examines the effectiveness of immunotherapy in metastatic solid tumours with PDL1 negative/TMB low/MSI stability. Methods: Study was carried out from Jan-2020 to Dec- 2022 (retrospective data from 2019 also included for analysis). Inclusion criteria: Metastatic solid tumours in patients who received immunotherapy. Exclusion criteria: PDL1>1% ( Either TPS/ CPS >1) by sp263 or 22c3 platforms, TMB> 10, Unstable MSI by IHC or by genomics. Patients who were diagnosed with melanoma, hepatocellular cancer, renal cell carcinoma were also excluded from the study. Response was initially assessed after 3 to 6 cycles of immunotherapy, analysed by PET CT scan. Data were analysed using standard statistical method. Results: After carefully applying exclusion criteria, a total of 40 patients were enrolled in the research, with a male to female ratio of 1.5. Overall response rate in all tumours was 17.5% (7/ 40) Immune checkpoint inhibitors' ORRs at various tumour locations. Among the responders head and neck tumours 2/4 (50%) and lung cancers (37.5%) had higher ORR who also had greater depth of response, living more than 2 years from diagnosis. There is no response observed in gastroesophageal (0/8) gynaecological malignancies (clear cell ovary (0/2), endometrial and cervical (0/3). A patient with urothelial carcinoma who also had a BRCA mutation and was one out of seven responded to IO. Conclusions: Regardless of the presence of PDL1 expression, high TMB, or MSI, adding immune checkpoint inhibitors to the treatment regimen for metastatic head and neck malignancies and lung tumours that lack driver mutations is obviously advantageous. On the other hand, immunotherapy had no effect on gastrointestinal, gynaecological, or urothelial tumours. To validate these findings, more research with several centres and a sizable sample size is necessary. It's interesting that one patient responded to immunotherapy with positive BRCA mutation. Investigating immunotherapy in HRR deficient tumours may shed further insights. [Table: see text]
Alkuraya-Kucinskas syndrome is a neurodevelopmental disorder due to mutation in KIAA1109 gene. We report a case of optic pathway tumor in a child with novel variant of KIAA1109. A plausible mechanism of gliomagenesis is considered based on influence of KIAA1109 on regulation of phosphatidyl inositol phosphorylation.
e13061 Background: In current clinical practice, the decision of using anti-HER2 targeted agents for breast cancer is based primarily on HER2 protein overexpression, assessed using immunohistochemistry and/or HER2 gene amplification on FISH assay(2018 ASCO/CAP guidelines). It is increasingly being recognized that HER2-negative breast cancer is characterized by a wide spectrum of HER2 expression, particularly important for the triple-negative breast cancer (TNBC) group, the treatment options for which are far less compared to hormone receptor-positive tumors. HER2-low breast cancer (HER1+ or 2+, without gene amplification) is an emerging subtype with differing clinicopathologic and prognostic implications. There is accumulating evidence that HER2-negative tumors may switch to HER2-low status and vice versa at tumor recurrence. The development of newer drug classes like antibody-drug conjugates and immunotherapy have created a window of opportunity for this sub-category of breast cancer. Methods: We aimed to evaluate HER2 0/normal and HER2-low expression in TNBCs, their clinicopathological characteristics, and prognostic significance. Clinical and laboratory data for 207 TNBC cases (184 non-metastatic and 23 metastatic) diagnosed between February 2010 and December 2019 was available for analysis and cases were followed up until December 2021. Androgen receptor (AR) immunohistochemistry was performed on available FFPE blocks. Results: Non-metastatic TNBCs: Median age was 50 (SD 11.77; range 23 to 82) years. 91.9% of HER2-low cases were more than 40years old compared to 70.1% of HER2 0 cases, p = 0.006. 79.9% were HER2 0, 14.1% were HER2 1+, and 6% were HER2 2+. 30.7% (39/127) of cases were AR+. Compared with HER2 0, HER2-low cases exhibited a lower histological grade (Her2 0 - Grade 3: 72.7%, Grade 2: 27.3%; Her2-low- Grade 3: 57.1%, Grade 2: 40%, Grade 1: 2.9% p=0.048). Compared with HER2 0, more of HER2-low cases were AR+ (For Her2 0 26.5% were AR+; For Her2-low 48% were AR+, p=0.036). There was no significant difference in disease-free survival between the two groups. There was no significant difference in overall survival (OS) between the two groups (Her2 0- Mean: 102.0 months, Median: Not achieved; Her2-low - Mean: 69.60 months, Median: 77.4 months p=0.73). Within the Her2-low group, patients ≤40 years had a median OS of 44.3 months. Metastatic TNBCs: Median age was 47 (SD 10.38; range 30 to 74) years. There was no significant correlation between the clinicopathological characteristics. No significant difference in OS was seen (Her2 0- Median: 44.9 months; Her2-low- Median: 24.3 months, p=0.20). Conclusions: The non-significant trend towards a lower survival for Her2-low TNBCs, coupled with a surprisingly lower histologic grade and a higher AR positivity needs to be further evaluated in larger studies. Further translational research to optimize treatment for this subgroup is needed.
Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factors (VEGF). It blocks the angiogenic molecule VEGF, thereby inhibiting tumor angiogenesis. It is approved for a range of solid cancers such as ovarian cancer, colorectal cancer, glioblastoma multiforme, advanced non-squamous non-small cell lung cancer (NSCLC), cervical cancer, renal cell carcinoma, and metastatic breast cancer.
'%3e%3ccircle r='20' fill='%23008'/%3e%3ccircle r='17.5' fill='%23fff'/%3e%3ccircle r='3.5' fill='%23008'/%3e%3cg id='d'%3e%3cg id='c'%3e%3cg id='b'%3e%3cg id='a' fill='%23008'%3e%3ccircle r='.875' transform='rotate(7.5 -8.75 133.5)'/%3e%3cpath d='M0 17.5.6 7 0 2l-.6 5L0 17.5z'/%3e%3c/g%3e%3cuse xlink:href='%23a' transform='rotate(15)'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='rotate(30)'/%3e%3c/g%3e%3cuse xlink:href='%23c' transform='rotate(60)'/%3e%3c/g%3e%3cuse xlink:href='%23d' transform='rotate(120)'/%3e%3cuse xlink:href='%23d' transform='rotate(-120)'/%3e%3c/g%3e%3c/svg%3e)