Oncologic Outcomes of Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer: A Single-institution Experience

Introduction: This study reports the outcomes of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation followed by surgery in a local population of Singapore. Materials and Methods: The records of 85 patients who underwent neoadjuvant chemoradiation for locally advanced rectal cancer followed by surgery at the Tan Tock Seng Hospital (TTSH) between November 2002 and January 2012 were reviewed. The treatment protocol comprised radiotherapy to a total dose of 50.4 Gy concurrent with 5-fluorouracil-based chemotherapy. Patients underwent total mesorectal excision surgery following the completion of neoadjuvant chemoradiation. Local control, disease-free survival and overall survival were analysed using Kaplan-Meier methods. Results: Median age of the patients was 61 years. All of them completed radiotherapy. One patient did not complete neoadjuvant chemotherapy. The median time to surgery was 52 days. Fifty-five percent (47 of 85) of patients achieved pathological down staging and 13% (11 of 85) of patients had a pathologic complete response to preoperative treatment. The neoadjuvant chemoradiation was well tolerated. Four percent of patients had grade 3 diarrhoea and 4% of them had grade 3 dermatitis. There were no grade 4 toxicities. With a median follow-up of 41 months, the 5-year actuarial local recurrence, disease-free survival and overall survival rates were 7%, 71.9%, % and 83.2% respectively. Univariate analysis showed that patients with positive surgical margins had significantly worse disease-free survival and overall survival (P = 0.012 and P <0.001 respectively) and a trend towards a higher rate of local recurrence (P = 0.08). Conclusion: Our study provides evidence that neoadjuvant chemoradiation is an effective treatment for locally advanced rectal cancer. Our outcomes are comparable with internationally published data and demonstrate the reproducibility of the neoadjuvant approach in an Asian population

Applying the ASCO and European Society for Medical Oncology Value Frameworks to Nasopharyngeal Cancer Treatments: Is Adding Induction Chemotherapy or Adjuvant Chemotherapy to Concurrent Chemoradiotherapy Worthwhile?

10.1200/OP.20.00413JCO ONCOLOGY PRACTICE1611755-

Care redesign of pelvic radiotherapy using Design Thinking: An enhanced quality improvement initiative.

10.1200/jco.2020.38.29_suppl.246Journal of Clinical Oncology3829_suppl246-24

Applying the ASCO and ESMO Value Frameworks to nasopharyngeal cancer treatments: Is adding induction chemotherapy or adjuvant chemotherapy to concurrent chemoradiotherapy worthwhile?

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Long-term outcomes after reirradiation in nasopharyngeal carcinoma with intensity-modulated radiotherapy: A meta-analysis

10.1002/hed.24993HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK403622-63

GAGE mediates radio resistance in cervical cancers via the regulation of chromatin accessibility

Radiotherapy (RT) resistance is a major cause of treatment failure in cancers that use definitive RT as their primary treatment modality. This study identifies the cancer/testis (CT) antigen G antigen (GAGE) as a mediator of radio resistance in cervical cancers. Elevated GAGE expression positively associates with de novo RT resistance in clinical samples. GAGE, specifically the GAGE12 protein variant, confers RT resistance through synemin-dependent chromatin localization, promoting the association of histone deacetylase 1/2 (HDAC1/2) to its inhibitor actin. This cumulates to elevated histone 3 lysine 56 acetylation (H3K56Ac) levels, increased chromatin accessibility, and improved DNA repair efficiency. Molecular or pharmacological disruption of the GAGE-associated complex restores radiosensitivity. Molecularly, this study demonstrates the role of GAGE in the regulation of chromatin dynamics. Clinically, this study puts forward the utility of GAGE as a pre-screening biomarker to identify poor responders at initial diagnosis and the therapeutic potential of agents that target GAGE and its associated complex in combination with radiotherapy to improve outcomes

GAGE mediates radio resistance in cervical cancers via the regulation of chromatin accessibility

Radiotherapy (RT) resistance is a major cause of treatment failure in cancers that use definitive RT as their primary treatment modality. This study identifies the cancer/testis (CT) antigen G antigen (GAGE) as a mediator of radio resistance in cervical cancers. Elevated GAGE expression positively associates with de novo RT resistance in clinical samples. GAGE, specifically the GAGE12 protein variant, confers RT resistance through synemin-dependent chromatin localization, promoting the association of histone deacetylase 1/2 (HDAC1/2) to its inhibitor actin. This cumulates to elevated histone 3 lysine 56 acetylation (H3K56Ac) levels, increased chromatin accessibility, and improved DNA repair efficiency. Molecular or pharmacological disruption of the GAGE-associated complex restores radiosensitivity. Molecularly, this study demonstrates the role of GAGE in the regulation of chromatin dynamics. Clinically, this study puts forward the utility of GAGE as a pre-screening biomarker to identify poor responders at initial diagnosis and the therapeutic potential of agents that target GAGE and its associated complex in combination with radiotherapy to improve outcomes

GAGE mediates radio resistance in cervical cancers via the regulation of chromatin accessibility

10.1016/j.celrep.2021.109621CELL REPORTS36