Optimizing Therapeutic Approaches in Superficial Esophageal Cancer: Reduced-volume Radiotherapy and Dose-dense Chemotherapy After Endoscopic Resection.

Background/aim: Endoscopic submucosal dissection (ESD) followed by chemoradiotherapy (CRT) has become a promising treatment modality in the management of early-stage superficial esophageal squamous cell carcinoma (SESCC). However, radiotherapy often leads to significant adverse events (AEs), including cardiopulmonary toxicity, limiting the delivery of this treatment modality. This study aimed to evaluate the efficacy of reduced-volume radiotherapy and dose-dense chemotherapy in mitigating AEs for high-risk SESCC following ESD.

Disparities in radiation therapy utilization for cancer patients in Victoria.

Introduction: To evaluate the proportion of cancer patients who received radiation therapy (RT) within 12 months of cancer diagnosis (RTU12) and identify factors associated with RTU12.

Methods: This is a population-based cohort of individuals with incident cancer, diagnosed between 2013 and 2017 in Victoria. Data linkages were performed between the Victorian Cancer Registry and Victorian Radiotherapy Minimum Dataset.

Machine learning predicts cancer subtypes and progression from blood immune signatures.

Clinical adoption of immune checkpoint inhibitors in cancer management has highlighted the interconnection between carcinogenesis and the immune system. Immune cells are integral to the tumour microenvironment and can influence the outcome of therapies. Better understanding of an individual's immune landscape may play an important role in treatment personalisation.

Temporal determinants of tumour response to neoadjuvant rectal radiotherapy.

Introduction: In locally advanced rectal cancer, longer delay to surgery after neoadjuvant radiotherapy increases the likelihood of histopathological tumour response. Chronomodulated radiotherapy in rectal cancer has recently been reported as a factor increasing tumour response to neoadjuvant treatment in patients having earlier surgery, with patients receiving a larger proportion of afternoon treatments showing improved response. This paper aims to replicate this work by exploring the impact of these two temporal factors, independently and in combination, on histopathological tumour response in rectal cancer patients.

Custom-designed Small Animal focal iRradiation Jig (SARJ): design, manufacture and dosimetric evaluation.

Objective: Preclinical animal models allow testing and refinement of novel therapeutic strategies. The most common preclinical animal irradiators are fixed source cabinet irradiators, which are vastly inferior to clinical linear accelerators capable of delivering highly conformal and precise treatments. The purpose of this study was to design, manufacture and test an irradiation jig (mall nimal focal iradiation ig, SARJ) that would enable focal irradiation of subcutaneous tumours in a standard fixed source cabinet irradiator.

Development of quality indicators to monitor radiotherapy care for men with prostate cancer: A modified Delphi method.

Background And Purpose: Quality indicators (QIs) have been developed for many aspects of prostate cancer care, but are under-developed with regard to radiotherapy treatment. We aimed to develop a valid, relevant and feasible set of core QIs to measure quality of radiotherapy care in men with prostate cancer.

Materials And Methods: We used a RAND-modified Delphi process to select QIs that were regarded as both important and feasible measures of quality radiotherapy care.

Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study.

Objective: For patients with locally advanced rectal cancer (LARC), adjuvant chemotherapy selection following surgery remains a major clinical dilemma. Here, we investigated the ability of circulating tumour DNA (ctDNA) to improve risk stratification in patients with LARC.

Design: We enrolled patients with LARC (T3/T4 and/or N+) planned for neoadjuvant chemoradiotherapy.

Does chronomodulated radiotherapy improve pathological response in locally advanced rectal cancer?

The predominant mode of radiation-induced cell death for solid tumours is mitotic catastrophe, which is in part dependent on sublethal damage repair being complete at around 6 h. Circadian variation appears to play a role in normal cellular division, and this could influence tumour response of radiation treatment depending on the time of treatment delivery. We tested the hypothesis that radiation treatment later in the day may improve tumour response and nodal downstaging in rectal cancer patients treated neoadjuvantly with radiation therapy.

Precision Medicine and Pancreatic Cancer: A Gemcitabine Pathway Approach.

Objectives: There is a need for validated predictive markers of gemcitabine response to guide precision medicine treatment in pancreatic cancer. We previously validated human equilibrative nucleoside transporter 1 as a predictive marker of gemcitabine treatment response using Radiation Therapy Oncology Group 9704. Controversy exists about the predictive value of gemcitabine metabolism pathway biomarkers: deoxycytidine kinase (DCK), ribonucleotide reductase 1 (RRM1), RRM2, and p53R2.

Development of Indicators to Assess Quality of Care for Prostate Cancer.

Background: The development, monitoring, and reporting of indicator measures that describe standard of care provide the gold standard for assessing quality of care and patient outcomes. Although indicator measures have been reported, little evidence of their use in measuring and benchmarking performance is available. A standard set, defining numerator, denominator, and risk adjustments, will enable global benchmarking of quality of care.

Expression of cyclin D1a and D1b as predictive factors for treatment response in colorectal cancer.

Background: The aim of this study was to investigate the value of the cyclin D1 isoforms D1a and D1b as prognostic factors and their relevance as predictors of response to adjuvant chemotherapy with 5-fluorouracil and levamisole (5-FU/LEV) in colorectal cancer (CRC).

Methods: Protein expression of nuclear cyclin D1a and D1b was assessed by immunohistochemistry in 335 CRC patients treated with surgery alone or with adjuvant therapy using 5-FU/LEV. The prognostic and predictive value of these two molecular markers and clinicopathological factors were evaluated statistically in univariate and multivariate survival analyses.

Cytidine deaminase single-nucleotide polymorphism is predictive of toxicity from gemcitabine in patients with pancreatic cancer: RTOG 9704.

The aim of this study is to validate the prognostic and predictive value of the non-synonymous cytidine deaminase (CDA) Lys²⁷Gln polymorphism for hematological toxicity and survival using a randomized phase III adjuvant trial (Radiation Therapy Oncology Group (RTOG) 9704) in pancreatic cancer in which one treatment arm received gemcitabine. CDA is involved in gemcitabine inactivation, and there is conflicting data on the role of the non-synonymous CDA Lys²⁷Gln polymorphism in predicting toxicity and survival in cancer patients treated with gemcitabine. RTOG 9704 randomized 538 patients after pancreatic resection to receive radiotherapy with either 5-fluorouracil (5-FU) or gemcitabine.

Alternative cyclin D1 splice forms differentially regulate the DNA damage response.

The DNA damage response (DDR) activates downstream pathways including cell cycle checkpoints. The cyclin D1 gene is overexpressed or amplified in many human cancers and is required for gastrointestinal, breast, and skin tumors in murine models. A common polymorphism in the human cyclin D1 gene is alternatively spliced, resulting in cyclin D1a and D1b proteins that differ in their carboxyl terminus.

Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer.

Background & Aims: The human equilibrative nucleoside transporter (hENT1) protein transports gemcitabine into cells. Small retrospective studies in pancreatic cancer suggest that levels of hENT1 protein or messenger RNA may have prognostic value. We studied the predictive value of hENT1 levels in a cohort of pancreatic adenocarcinoma patients from the large prospective randomized adjuvant treatment trial RTOG9704.

Differences in toxicity across gender in patients treated with chemoradiation for rectal cancer.

The primary objective was to prospectively investigate the efficacy and toxicity of bolus 5-fluorouracil (5-FU) chemotherapy compared with the infusional 5-FU in combination with preoperative radiation in patients with locally advanced rectal cancer. Furthermore, in light of previous reports, toxicity profiles between men and women were also compared. Eighty-four consecutive patients with rectal adenocarcinoma were prospectively treated.

Early detection markers in Pancreas Cancer.

The role of early detection in cancer has shown improved survival for certain cancers, including colon cancer, cervical cancer and breast cancer. The possibility for early detection of pancreatic cancer may be realized by an improved understanding of the histology and molecular genetics of precursor lesions and cancerous lesions in pancreatic cancer and the development of sensitive and specific screening tests (both invasive and non-invasive) to detect early pancreatic cancer. The NIH-NCI Early Detection Research Network (EDRN) in Pancreatic Cancer has been focussed on the development and validation of new biomarkers for the detection of early pancreatic cancer.

Radiation modifiers: treatment overview and future investigations.

Many radiosensitizers are in current clinical use. In addition, a myriad of potential new targeted therapies, which may also interact with radiation, are in clinical development. The clinical utility of new targeted therapies, in combination with existing radiation sensitizers (chemotherapies) requires further evaluation, as does the understanding of their acute and late radiation effects.

Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.

Background: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity.

The efficacy of hyperbaric oxygen therapy in the treatment of radiation-induced late side effects.

Purpose: We investigated the efficacy of hyperbaric oxygen therapy (HBOT) in the management of patients with radiation-induced late side effects, the majority of whom had failed previous interventions.

Methods And Materials: Of 105 eligible subjects, 30 had either died or were not contactable, leaving 75 who qualified for inclusion in this retrospective study. Patients answered a questionnaire documenting symptom severity before and after treatment (using Radiation Therapy Oncology Group criteria), duration of improvement, relapse incidence, and HBOT-related complications.

CpG island methylator phenotype is an independent predictor of survival benefit from 5-fluorouracil in stage III colorectal cancer.

Purpose: The CpG island methylator phenotype (CIMP) is observed in approximately 30% of colorectal cancer (CRC) cases and is characterized by the concurrent methylation of multiple CpG islands in tumor DNA. This phenotype (CIMP+) is more frequently observed in tumors with proximal location, microsatellite instability, and normal p53. Because it has previously been observed that each of these features is associated with a good survival benefit from 5-fluorouracil (5-FU)-based adjuvant chemotherapy, we investigated in the present study whether CIMP+ has independent predictive value.

Prognostic significance of microsatellite instability and Ki-ras mutation type in stage II colorectal cancer.

Objectives: The survival of stage II colorectal cancer (CRC) patients is approximately 70% at 5 years. Identification of the patient subgroup at high risk for tumour recurrence and death would allow more informed use of chemotherapy for this stage of disease. Several clinical and pathological factors have been reported to associate with worse survival.