Long-term remission after low dose radiotherapy in patient with extensive squamous cell carcinoma of the hand: A case report

10.1097/MD.0000000000005013MEDICINE953

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

Does external beam radiation boost to pelvic lymph nodes improve outcomes in patients with locally advanced cervical cancer?

10.1186/s12885-019-5594-4BMC CANCER191complete

Does external beam radiation boost to pelvic lymph nodes improve outcomes in patients with locally advanced cervical cancer?

Abstract Background Current recommendation for locally advanced cervical cancer includes pelvic external beam radiation therapy (EBRT) with concurrent chemotherapy followed by brachytherapy. Involvement of pelvic lymph nodes is an important prognostic factor in locally advanced cervical cancer and recurrence commonly occurs despite definitive treatment. To date, there is no standard guideline on whether an EBRT boost should be applied to involved pelvic lymph nodes. Our study aims to assess if pelvic EBRT boost would reduce recurrence, benefit survival, and affect associated toxicities. Methods We conducted a retrospective review of locally advanced cervical cancer cases treated with definitive treatment at our institution. Involvement of pelvic lymph nodes were assessed on CT, MRI (> 10 mm or suspicious features) or PET scan (SUVmax > 2.5). EBRT dose ranged from 45 to 50.4 Gy with nodal boost ranging from 3.6–19.8 Gy. Results Between 2008 to 2015, 139 patients with locally advanced cervical cancer underwent treatment. Sixty-seven patients had positive pelvic lymph nodes, of which 53.7% received a nodal boost. Five-year recurrence free survival was 48.6% with vs. 64.5% without nodal boost (P = 0.169) and 5-year overall survival in those with positive pelvic lymph nodes was 74.3% with vs. 80.6% without nodal boost (P = 0.143). There was no significant difference in toxicity with nodal boost. Conclusions EBRT boost to pelvic lymph nodes does not reduce recurrence or improve survival in locally advanced cervical cancer with lymph node involvement at diagnosis

Palliative radiotherapy for gastric cancer: a systematic review and meta-analysis

10.18632/oncotarget.15554ONCOTARGET81525797-2580

Navigating the challenges of the COVID-19 outbreak: Perspectives from the radiation oncology service in Singapore

10.1016/j.radonc.2020.03.030RADIOTHERAPY AND ONCOLOGY148189-19

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