Automated assessment of CD8+ T-lymphocytes and stroma fractions complement conventional staging of colorectal cancer.

BACKGROUND: Tumor development is critically dependent on the supporting stroma consisting of inflammatory cells and fibroblasts. This study intended to improve prognostic prediction for early colorectal cancer (CRC) by combined estimation of T-lymphocyte and stroma fractions with conventional markers. METHODS: In total 509 and 1041 stage II/ΙΙΙ CRC from the VICTOR and QUASAR 2 trials were included as a training set and a validation set, respectively. Intratumoral CD8+ T-lymphocytes and stroma were identified and quantified by machine-based learning on digital sections. The primary endpoint was to evaluate the prognostic value of the combined marker for time to recurrence (TTR). FINDINGS: For low-risk patients (n = 598; stage Ⅱ, and stage ΙΙΙ pT1-3 pN1 with neither lymphatic (L-) nor vascular (V-) invasion), low stroma fraction (n = 511) identified a good prognostic subgroup with 5-year TTR of 86% (95% CI 83-89), versus the high stroma subgroup TTR of 78% (HR = 1.75, 95% CI 1.05-2.92; P = 0.029). For high-risk patients (n = 394; stage ΙΙΙ pT3 pN1 L+/V+, pT4, or pN2), combined low CD8+ and high stroma fraction identified a poor prognostic subgroup (n = 34) with 5-year TTR of 29% (95% CI 17-50), versus the high CD8+ fraction and low stroma fraction subgroup (n = 138) of 64% (HR = 2.86, 95% CI 1.75-4.69; P < 0.001). INTERPRETATION: Quantification of intratumoral CD8+ T-lymphocyte and stroma fractions can be combined with conventional prognostic markers to improve patient stratification.

Delivering Cancer Care During the COVID-19 Pandemic: Recommendations and Lessons Learned From ASCO Global Webinars.

PURPOSE: In response to the COVID-19 pandemic, the ASCO launched a Global Webinar Series to address various aspects of cancer care during the pandemic. Here we present the lessons learned and recommendations that have emerged from these webinars. METHODS: Fifteen international health care experts from different global regions and oncology disciplines participated in one of the six 1-hour webinars to discuss the latest data, share their experiences, and provide recommendations to manage cancer care during the COVID-19 pandemic. These sessions include didactic presentations followed by a moderated discussion and questions from the audience. All recommendations have been transcribed, categorized, and reviewed by the experts, who have also approved the consensus recommendations. RESULTS: The summary recommendations are divided into different categories, including risk minimization; care prioritization of patients; health care team management; virtual care; management of patients with cancer undergoing surgical, radiation, and systemic therapy; clinical research; and recovery plans. The recommendations emphasize the protection of patients and health care teams from infections, delivery of timely and appropriate care, reduction of harm from the interruption of care, and preparation to handle a surge of new COVID-19 cases, complications, or comorbidities thereof. CONCLUSION: The recommendations from the ASCO Global Webinar Series may guide practicing oncologists to manage their patients during the ongoing pandemic and help organizations recover from the crisis. Implementation of these recommendations may improve understanding of how COVID-19 has affected cancer care and increase readiness to manage the current and any future outbreaks effectively.

Prognostic value of DNA ploidy and automated assessment of stroma fraction in prostate cancer.

The combination of DNA ploidy and automatically estimated stroma fraction has been shown to correlate with recurrence and cancer death in colorectal cancer. We aimed to extend this observation and evaluate the prognostic importance of this combined marker in prostate cancer. DNA ploidy status was determined by image cytometry and the stroma fraction was estimated automatically on hematoxylin and eosin stained sections in three tumor samples from each patient to account for tumor heterogeneity. The optimal threshold for low (≤56%) and high (>56%) stroma fraction was identified in a discovery cohort (n = 253). The combined marker was validated in an independent patient cohort (n = 259) with biochemical recurrence as endpoint. The combined marker predicted biochemical recurrence independently in the validation cohort. Multivariable analysis showed that the highest risk of recurrence was observed for patients with samples that had both non-diploid ploidy status and a high stroma fraction (hazard ratio: 2.51, 95% confidence interval: 1.18-5.34). In conclusion, we suggest the combination of DNA ploidy and automatically estimated stroma fraction as a prognostic marker for the risk stratification of prostate cancer patients. It may also be a potential generic marker as concurrent results have been described in colorectal cancer.

Strategies for Sustainable Cancer Care.

There is an increasing focus on the relative cost-effectiveness and sustainability of delivering high-quality cancer care, with most emphasis, debatably, given to cost control of innovative treatments. It is difficult to calculate all the direct and indirect contributors to the total cost of cancer treatment, but it is estimated that cancer drugs constitute 10% to 30% of the total cost of cancer care. A 2007 study in France showed the contribution of drug costs was less than 20%, with approximately 70% of the total expenditure on cancer accounted for by health care resource use, such as hospitalization. The U.K. government established the National Institute for Health and Care Excellence (NICE)-the dominant function of which is technology appraisal-to assess the clinical and cost-effectiveness of new pharmaceutical and biopharmaceutical products. This is to ensure that all National Health Service (NHS) patients have equitable access to the most clinically effective and cost-effective treatments that are viable. NICE has developed a transparent, public process to judge incremental cost-effectiveness using the quality-adjusted life year (QALY), which allows comparisons of cost-effectiveness across medical specialties. NICE has been both lauded and criticized-especially when it passes judgment on marginally effective but expensive anticancer drugs-but it provides a route to "rational rationing" and, therefore, may contribute to sustainable cancer care by highlighting the issue of affordable medicine. This implies a challenge to the wider oncology community as to how we might cooperate to introduce the concept of value-driven cancer care.

Building capacity for sustainable research programmes for cancer in Africa.

Cancer research in Africa will have a pivotal role in cancer control planning in this continent. However, environments (such as those in academic or clinical settings) with limited research infrastructure (laboratories, biorespositories, databases) coupled with inadequate funding and other resources have hampered African scientists from carrying out rigorous research. In September 2012, over 100 scientists with expertise in cancer research in Africa met in London to discuss the challenges in performing high-quality research, and to formulate the next steps for building sustainable, comprehensive and multi-disciplinary programmes relevant to Africa. This was the first meeting among five major organizations: the African Organisation for Research and Training in Africa (AORTIC), the Africa Oxford Cancer Foundation (AfrOx), and the National Cancer Institutes (NCI) of Brazil, France and the USA. This article summarizes the discussions and recommendations of this meeting, including the next steps required to create sustainable and impactful research programmes that will enable evidenced-based cancer control approaches and planning at the local, regional and national levels.

Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer.

PURPOSE: We developed quantitative gene expression assays to assess recurrence risk and benefits from chemotherapy in patients with stage II colon cancer. PATIENTS AND METHODS: We sought validation by using RNA extracted from fixed paraffin-embedded primary colon tumor blocks from 1,436 patients with stage II colon cancer in the QUASAR (Quick and Simple and Reliable) study of adjuvant fluoropyrimidine chemotherapy versus surgery alone. A recurrence score (RS) and a treatment score (TS) were calculated from gene expression levels of 13 cancer-related genes (n = 7 recurrence genes and n = 6 treatment benefit genes) and from five reference genes with prespecified algorithms. Cox proportional hazards regression models and log-rank methods were used to analyze the relationship between the RS and risk of recurrence in patients treated with surgery alone and between TS and benefits of chemotherapy. RESULTS: Risk of recurrence was significantly associated with RS (hazard ratio [HR] per interquartile range, 1.38; 95% CI, 1.11 to 1.74; P = .004). Recurrence risks at 3 years were 12%, 18%, and 22% for predefined low, intermediate, and high recurrence risk groups, respectively. T stage (HR, 1.94; P < .001) and mismatch repair (MMR) status (HR, 0.31; P < .001) were the strongest histopathologic prognostic factors. The continuous RS was associated with risk of recurrence (P = .006) beyond these and other covariates. There was no trend for increased benefit from chemotherapy at higher TS (P = .95). CONCLUSION: The continuous 12-gene RS has been validated in a prospective study for assessment of recurrence risk in patients with stage II colon cancer after surgery and provides prognostic value that complements T stage and MMR. The TS was not predictive of chemotherapy benefit.

Open access chemical and clinical probes to support drug discovery.

Drug discovery resources in academia and industry are not used efficiently, to the detriment of industry and society. Duplication could be reduced, and productivity could be increased, by performing basic biology and clinical proofs of concept within open access industry-academia partnerships. Chemical biologists could play a central role in this effort.

Intrahepatic arterial versus intravenous fluorouracil and folinic acid for colorectal cancer liver metastases: a multicentre randomised trial.

BACKGROUND: The liver is the most frequent site for metastases of colorectal cancer, which is the second largest contributor to cancer deaths in Europe. We did a randomised trial to compare an intrahepatic arterial (IHA) fluorouracil and folinic acid regimen with the standard intravenous de Gramont fluorouracil and folinic acid regimen for patients with adenocarcinoma of the colon or rectum, with metastases confined to the liver. METHODS: We randomly allocated 290 patients from 16 centres to receive either intravenous chemotherapy (folinic acid 200 mg/m2, fluorouracil bolus 400 mg2 and 22-h infusion 600 mg/m2, day 1 and 2, repeated every 14 days), or IHA chemotherapy designed to be equitoxic (folinic acid 200 mg/m2, fluorouracil 400 mg/m2 over 15 mins and 22-h infusion 1600 mg/m2, day 1 and 2, repeated every 14 days). The primary endpoint was overall survival, and analysis was by intention to treat. FINDINGS: 50 (37%) patients allocated to IHA did not start their treatment, and another 39 (29%) had to stop before receiving six cycles of treatment because of catheter failure. The IHA group received a median of two cycles (0-6), compared with 8.5 (6-12) for the intravenous group. 45 (51%) IHA patients who did not start or did not receive six cycles switched to intravenous treatment. In both groups, grade 3 or 4 toxicity was uncommon. Median overall survival was 14.7 months for the IHA group and 14.8 months for the intravenous group (hazard ratio 1.04 [95% CI 0.80-1.33], log-rank test p=0.79). Similarly, there was no significant difference in progression-free survival. INTERPRETATION: Our results showed no evidence of an advantage in progression-free survival or overall survival for the IHA group; thus continued use of this regimen cannot be recommended outside of a clinical trial.