Tumor molecular profiling of responders and non-responders following pembrolizumab monotherapy in chemotherapy resistant advanced cervical cancer.

Optimal treatment for advanced cervical cancer after first line chemotherapy remains undefined. Immune checkpoint inhibition with pembrolizumab, a programmed cell death protein 1(PD-1) inhibitor, is under investigation. We analyzed the micro-environmental and molecular genetic profile of tumors from 4 patients with metastatic cervical cancer treated with off-label second-line pembrolizumab in an effort to identify predictive biomarkers. All patients received 2 mg/kg of pembrolizumab, 3-weekly until disease progression. Immunohistochemistry(IHC) for PD-1, PD-L1, CD3 and CD8, as well as next generation sequencing (NGS) for 50 cancer-related genes were performed on tumor samples. All patients tolerated treatment well with no discontinuation of treatment due to toxicity. One patient experienced dramatic and prolonged partial response, and remains stable on pembrolizumab with a progression free survival (PFS) of 21 months at the time of reporting of this series. Three patients experienced disease progression as best response. In the exceptional responder, there was no tumoral expression of PD-L1, however, combined positive score (CPS) for PD-L1 was 1 and we identified somatic mutations in ERBB4(R612W), PIK3CA(E542K) and RB1(E365K). In 2 patients, despite progressive disease defined by RECIST v1.1, symptom stabilization on pembrolizumab was observed. The tumors of both patients had PD-1 expression in ≥1% of stromal lymphocytes. All patients with response or clinical benefit had CPS for PD-L1 ≥ 1. NGS revealed PIK3CA mutations in 3 tumors. Pembrolizumab is a promising therapeutic option in advanced cervical cancer. Further evaluation of biomarkers may guide optimal patient selection.

Does initial routine use of a compression garment reduce the risk of lower limb lymphedema after gynecological cancer treatment? A randomized pilot study in an Asian institution and review of the literature.

This is a randomized pilot study evaluating the effectiveness of customized compression garments (CG) in reducing the risk of lower limb lymphedema (LLL) in gynecological cancer patients. Patients who completed pelvic node dissection or radiation were routinely educated on reducing the risk of LLL by good skin care and manual lymphatic massage. After baseline lower limb volume perometry and clinical assessment, they were randomized to customized compression garment (CG) for 6 weeks (26 patients) or observation (30 patients). Both groups were followed up for 2 years and the primary outcome was the development of LLL. LLL incidence in the control group was 13.3% (4 of 30 patients) compared to 7.7% (2 of 26 patients) in the CG group. However the difference was not statistically significant (P=0.496). In the control group, 10.7% (3/28) who underwent node dissection developed LLL vs 7.7% (2/26) in the CG group. Among patients with node dissection plus radiation, LLL incidence was 14.3% (1/7) in the control group vs 12.5% (1/8) in the CG group. The mean onset of LLL was 12 months; compliance to CG wearing was high and QOL scores were similar in both groups. Customized low-compression CG worn for 6 weeks may have a possible benefit in reducing the risk of LLL when added to patient education on risk reduction although statistic significance was not achieved in this small pilot study. A larger multi-center study would be justified to expand these findings.

Adjuvant radiotherapy for endometrial cancer--a comparative review of radiotherapy technique with acute toxicity.

OBJECTIVES: The addition of pelvic radiotherapy to brachytherapy (EBRT-BT) in early-stage endometrial cancer is controversial and may cause unnecessary toxicity. The incidence of acute toxicity of EBRT-BT will have an impact on clinical decision and patient compliance but is currently poorly understood. This study compares the acute toxicities of EBRT-BT versus BT alone. MATERIALS AND METHODS: Seventy-nine patients with FIGO Stage IA-II endometrial cancer who underwent adjuvant radiotherapy, (EBRT-BT or BT alone) from 2001 to 2011 were included in the study. Medical records of these patients were reviewed retrospectively and toxicity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Patients were followed up for at least three months post-treatment to assess resolution of toxicity. RESULTS: The mean age of the study group was 60.6 years. Median follow-up was four years. Forty patients received EBRT-BT. There was a 37% increase in Grade 1-3 diarrhea with the addition of pelvic radiotherapy (OR 18.67, p < 0.0005) and a 34% increase in lethargy (p < 0.0005). There was also an increased occurrence of genitourinary and skin toxicities. Two patients in the EBRT-BT group required hospitalisation for severe diarrhea and three patients were unable to complete the treatment. All acute toxicities had resolved by three months post treatment. CONCLUSION: EBRT-BT causes significantly more acute toxicities compared to BT alone. Patients should be informed of this during counselling.

Hypofractionated accelerated radiotherapy with concurrent carboplatin for locally advanced squamous cell carcinoma of the head and neck.

AIMS: Hypofractionated accelerated radiotherapy with concurrent carboplatin utilises both advantages of altered fractionation and synchronous chemotherapy to maximise local control in locally advanced head and neck cancer. Such fractionation schedules are increasingly used in the intensity-modulated radiotherapy era and the aim of this study was to determine the outcome of hypofractionated accelerated radiotherapy with carboplatin. MATERIALS AND METHODS: One hundred and fifty consecutive patients with squamous cell carcinoma of the larynx, oropharynx, oral cavity and hypopharynx (International Union Against Cancer [IUAC] stage II-IV) treated with 55Gy in 20 fractions over 25 days with concurrent carboplatin were analysed. Outcome measures were 2 year overall survival, local control and disease-free survival. RESULTS: The median follow-up in surviving patients was 25 months. IUAC stages: II n=15; III n=42; IV n=93. Two year overall survival for all patients was 74.9% (95% confidence interval 66.0-81.7%). Two year local control was 78.3% (95% confidence interval 69.6-84.8%). Two year disease-free survival was 67.2% (95% confidence interval 58.3-74.7%). There were 135 patients with stage III and IV disease. For these patients, the 2 year overall survival, local control and disease-free survival were 74.3% (95% confidence interval 64.7-81.6%), 79.1% (95% confidence interval 69.8-85.9%) and 67.6% (95% confidence interval 58.0-75.4%), respectively. Prolonged grade 3 and 4 mucositis seen at ≥4 weeks were present in 9 and 0.7%, respectively. Late feeding dysfunction (determined by dependence on a feeding tube at 1 year) was seen in 13% of the surviving patients at 1 year. CONCLUSION: Hypofractionated accelerated radiotherapy with concurrent carboplatin achieves a high local control. This regimen should be considered for a radiotherapy dose-escalation study using intensity-modulated radiotherapy.