2021 ASCO: Two new research directions for pancreatic cancer

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2021 ASCO: Two new research directions for pancreatic cancer

2021 ASCO: Two new research directions for pancreatic cancer.  At the ASCO conference in 2021, what is the new progress in the research of advanced pancreatic ductal adenocarcinoma and locally advanced pancreatic cancer?

Pancreatic cancer is one of the most malignant tumors of the digestive tract, with insidious onset and rapid progress [1]. Early diagnosis of pancreatic cancer is difficult. Most patients are already at an advanced stage when they are diagnosed, and have lost the opportunity for surgery. Even if the patient undergoes surgical resection, the 5-year survival rate is still less than 20%, and the prognosis is not optimistic [1,2].

In recent years, with the continuous improvement of medical standards, the field of pancreatic cancer treatment has made rapid progress. This article provides professional explanations and comments on the two research results announced at the 2021 American Society of Clinical Oncology (ASCO) meeting.

ctDNA plasma analysis guides clinical decision-making in advanced pancreatic cancer and helps predict clinical prognosis

Pancreatic ductal adenocarcinoma (PDAC) accounts for about 90% of the incidence of pancreatic cancer, and its therapeutic effect and prognosis are extremely poor. Surgical resection is currently the only effective treatment method, but unfortunately, many patients are already at an advanced stage when discovered, and only 20%-30% of patients have the opportunity of surgical resection [3].

Therefore, the early diagnosis of tumors is very important. However, there is no reliable screening tool to identify high-risk patients. In recent years, blood biomarkers in the form of DNA have shown great potential for cancer diagnosis and treatment plan guidance. Circulating tumor DNA (ctDNA) has gradually become a new potential detection method that can verify PDAC from non-malignant diseases. .

A retrospective analysis of the ASCO Conference in 2021 included 104 PDAC patients treated at Miaoyou Medical International Clinic, and 140 samples were collected. During the routine clinical diagnosis and treatment from 2017 to 2020, all patients underwent ctDNA analysis. . The study analyzed the correlation between progression-free survival (PFS) and overall survival (OS) and ctDNA test results [4].

The results of the study showed that the metastasis of PDAC in various parts (liver, bone, lung, peritoneum) is related to biomarkers such as KRAS and TP53.

Figure 1. The relationship between the incidence of metastasis in each site and the existence of mutations

Two or more system mutations are associated with shorter PFS and OS, which may mean that PDAC patients with genetic mutations have a worse prognosis.

Figure 2. The relationship between PFS, OS and mutations

Compared with locally advanced disease, CCND2, SMAD, KRAS and TP53 mutations are more likely to appear in metastatic disease.

Figure 3. Relationship between gene mutation and disease stage

Therefore, when patients with advanced PDAC cannot undergo pathological biopsy, ctDNA plasma analysis based on next-generation sequencing is a viable alternative method. ctDNA plasma analysis can collect comprehensive genomic data and has a potentially important impact on the guidance of real-time treatment plans for PDAC patients. , Help predict the long-term prognosis.

For ctDNA plasma analysis, pathological biopsy is the gold standard for diagnosing pancreatic cancer. Although traditional tissue biopsy can provide valuable information, pancreatic tissue sampling is difficult, invasive, and impossible to repeat biopsy, which greatly limits real-time monitoring and application personalization Opportunities for drugs.

Patients urgently need a minimally invasive, effective, simple and easy method for early diagnosis, prognostic stratification and tumor monitoring. Liquid biopsy is convenient for sampling, can obtain more comprehensive biological characteristics and information in the sample, and has a good prospect in the early diagnosis of advanced PDAC and the prediction of curative effect.

However, liquid biopsy also has problems and challenges. Improving specificity and sensitivity is the next goal of liquid biopsy.

The standard treatment plan for locally advanced pancreatic cancer is still being explored, and translational therapy has become a research hotspot

Although more than 40% of pancreatic cancer patients have no distant metastasis, they are accompanied by extensive vascular and lymph node invasion and cannot receive timely surgical treatment. This stage of tumor is also called locally advanced pancreatic cancer (LAPC).

At present, for LAPC patients, systematic chemotherapy is the main treatment plan [5]. Some previous research reports have confirmed the efficacy of FOLFIRINOX (leucovorin, fluorouracil, irinotecan and oxaliplatin) and AG (gemcitabine and albumin-bound paclitaxel) for the treatment of LAPC, but there is no comparison of the efficacy of these two regimens. Randomized controlled trial.

In order to choose the best LAPC chemotherapy regimen, this year’s ASCO annual meeting announced a randomized phase II trial (JCOG1407), which compared the difference in efficacy between modified FOLFIRINOX (mFOLFIRINOX) and AG two chemotherapy regimens in LAPC patients [6] .

The study included 126 patients from Japanese medical institutions and randomly assigned to mFOLFIRINOX group (group A) (n=62) or AG group (group B) (n=64) for treatment. The results showed that the 1-year OS rate in group B was higher (77.4% vs. 82.5%), but the two-year OS rate in group A was higher (48.2 vs. 39.7%). Data on PFS and objective remission rate between the two groups There is no significant difference, so it takes longer time and more data to clarify the standard treatment plan for LAPC.

Figure 4. OS, PFS and DMFS of Group A and Group B

Figure 5. Objective remission rate and CA19-9 remission rate of group A and group B

LAPC was previously considered to be unresectable pancreatic cancer. With the development of neoadjuvant therapy, some LAPC patients can obtain surgical opportunities through neoadjuvant therapy. Combined with the results of clinical research of JCOG1407, more and more people are beginning to pay attention to the conversion therapy of unresectable LAPC patients. , 20% of LAPC patients can achieve R0 resection through conversion therapy, but most patients still cannot successfully convert to surgery.

At present, the commonly used treatment options for LAPC are FOLFIRINOX and AG, and the difference in objective effectiveness between the two is not significant. Regarding the choice of treatment plan, there is still no clear clinical standard.

Based on the heterogeneity of pancreatic cancer, 60% of patients’ tumor tissue is rich in fibrous tissue. The AG scheme may be more suitable for pancreatic cancer that is rich in fibrous tissue, and the FOLFIRINOX scheme may be more suitable for pancreatic cancer with a low proportion of fibrous tissue. Clinicians may be able to choose personalized treatment plans according to the different pathological characteristics of patients, and look forward to further research and exploration. “

Looking forward to the research direction of pancreatic cancer:

Early screening and Molecular classification

Most patients with pancreatic cancer are already at an advanced stage when they are diagnosed, and they have lost the opportunity for surgery. Therefore, it is necessary to achieve early screening for pancreatic cancer.

On the one hand, it is necessary to identify the population at high risk of pancreatic cancer, so as to reduce the scope of screening objects; on the other hand, it is necessary to improve the accuracy of CT and other imaging methods to increase the detection rate of pancreatic cancer.

In addition, liquid biopsy is becoming more and more popular in cancer diagnosis, prognostic judgment and monitoring. Finding new biomarkers in the body fluid of patients with pancreatic cancer has great development prospects for early diagnosis of the disease.

In lung cancer and breast cancer, the use of targeted therapies based on tumor molecular subtypes can improve the treatment effect and improve the survival of patients, which provides a basis for precision medicine for tumors.

Due to the heterogeneity of pancreatic cancer, a series of studies have carried out molecular classification of pancreatic cancer, and molecular classification will bring new hope for individualized and precise targeted therapy of pancreatic cancer patients.

It is expected that with the continuous advancement of molecular diagnostic technology, the clinical classification diagnosis, individualized treatment, and prognosis evaluation of pancreatic cancer will reach new heights. The diagnosis and treatment of pancreatic cancer is progressing slowly. Genetic testing and translational therapy may be one of the breakthroughs in future treatment.

The diagnosis and treatment of pancreatic cancer still has a long way to go, and further exploration is needed.

2021 ASCO: Two new research directions for pancreatic cancer

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