Combinatorial Hypofractionated Radiotherapy and Pembrolizumab in Anaplastic Thyroid Cancer.

Objectives Anaplastic thyroid cancer (ATC) is an aggressive disease associated with poor outcomes and resistance to therapies. Our study aim was to evaluate the activity of a combinatorial regimen of sandwich sequencing of pembrolizumab immunotherapy and hypofractionated radiotherapy (RT). Methods In this case series, patients with ATC received hypofractionated RT (QUAD-shot) and intravenous pembrolizumab 200mg every 3-4 weeks. Pembrolizumab was continued until disease progression or up till 24 months. Concurrent Lenvatinib treatment was allowed. Primary endpoint was best overall response (BOR) and progression-free survival (PFS). Additionally, we performed immune profiling of circulating T cells in a responder to investigate the immune response to our combinatorial treatment. Results At median follow-up of 32.6 months (IQR: 26.4-38.8), of a cohort of 5 patients, BOR was 80%; with 2 complete responses (CR) and 2 partial responses (PR). Patients who achieved CR remained disease-free at last follow-up. Median PFS was 7.6 months (IQR: 6.2-NR), and 1-year PFS and overall survival rate was 40% (95% CI: 13.7-100) for both. Treatment was well-tolerated, with mostly grade 1-2 adverse events. Immune profiling of one partial responder revealed an increase in activated CD4 and CD8 T cells post-QUAD-shot RT, which was further enhanced during the maintenance phase of pembrolizumab. Conclusions Herein, we reported a case series of 5 patients with ATC, with 2 long-term survivors who were treated with surgical debulking followed by QUAD-shot RT and pembrolizumab, possibly due to synergy of local and systemic treatments in activating anti-tumour immunogenic cytotoxicity. This regimen warrants further investigation in a larger cohort of patients.

Predicting outcomes for locally advanced rectal cancer treated with neoadjuvant chemoradiation with CT-based radiomics.

A feasibility study was performed to determine if CT-based radiomics could play an augmentative role in predicting neoadjuvant rectal score (NAR), locoregional failure free survival (LRFFS), distant metastasis free survival (DMFS), disease free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). The NAR score, which takes into account the pathological tumour and nodal stage as well as clinical tumour stage, is a validated surrogate endpoint used for early determination of treatment response whereby a low NAR score (< 8) has been correlated with better outcomes and high NAR score (> 16) has been correlated with poorer outcomes. CT images of 191 patients with LARC were used in this study. Primary tumour (GTV) and mesorectum (CTV) were contoured separately and radiomics features were extracted from both segments. Two NAR models (NAR > 16 and NAR < 8) models were constructed using Least Absolute Shrinkage and Selection Operator (LASSO) and the survival models were constructed using regularized Cox regressions. Area under curve (AUC) and time-dependent AUC were used to quantify the performance of the LASSO and Cox regression respectively, using ten folds cross validations. The NAR > 16 and NAR < 8 models have an average AUCs of 0.68 ± 0.13 and 0.59 ± 0.14 respectively. There are statistically significant differences between the clinical and combined model for LRFFS (from 0.68 ± 0.04 to 0.72 ± 0.04), DMFS (from 0.68 ± 0.05 to 0.70 ± 0.05) and OS (from 0.64 ± 0.06 to 0.66 ± 0.06). CTV radiomics features were also found to be more important than GTV features in the NAR prediction model. The most important clinical features are age and CEA for NAR > 16 and NAR < 8 models respectively, while the most significant clinical features are age, surgical margin and NAR score across all the four survival models.

Implications of HER2 amplification in small, node-negative breast cancers: do Asians differ?

BACKGROUND: We investigated the implications of HER2 amplification in Asian women with small, node-negative breast cancer in low- and middle-income countries (LMCs). METHODS: We reviewed the charts patients treated between 1989 and 2009 with breast conservation therapy for node-negative breast cancers measuring ≤ 2 cm. Disease-free survival (DFS), ipsilateral breast tumor recurrence (IBTR), distant disease-free survival (DDFS), and overall survival (OS) rates were estimated using the Kaplan-Meier method and were compared by the log-rank test. Potential covariates-age, tumor grade, hormone receptor status--were analyzed by multivariate analysis. RESULTS: A total of 519 patients were studied including 204 (39%) and 315 (61%) patients diagnosed with pT1ab and pT1c tumors, respectively. Median follow-up was 57 months. HER2 amplification was found in 17.1% of all patients and in 16.7% patients with pT1ab tumors. Among patients with T1ab tumors, 73.0 and 9.3% underwent adjuvant hormonal and chemotherapy, respectively; 3 of 34 T1ab patients with HER2-amplified tumors received trastuzumab. HER2 amplification was associated with poorer 5-year DFS (83.7% vs. 95.5%, P < 0.0001), DDFS (87.5% vs. 97.9%, P < 0.0001), and IBTR (8.6% vs. 2.1%, P < 0.0001) rates in patients with pT1 tumors. Multivariate analysis showed that HER2 amplification remained a significant negative prognostic factor for DFS [hazard ratio (HR) 4.1, 95% confidence interval (CI) 2.1-7.8, P < 0.0001], DDFS (HR 6.3, 95% CI 2.4-17.0, P < 0.0001), and IBTR (HR 4.5, 95% CI 2.0-10.0, P < 0.0001) rates. In the pT1ab subgroup, univariate analysis showed that HER2 amplification prognosticated for DFS (85.1% vs. 95.7%, P = 0.022) and IBTR (14.9% vs. 3.5%, P = 0.004) rates but not for the OS (100% vs. 99.2%, P = 0.487) rate. Similar results were obtained after excluding patients given trastuzumab. CONCLUSIONS: The decision to use trastuzumab in HER2-amplified pT1ab tumors must balance their poor outcome against intrinsic financial limitations in LMCs. Patient selection criteria needs fine-tuning, and resource-sensitive regimens must be explored.