• management
• neoadjuvant therapy
• pancreatic cancer
• pancreatic ductal adenocarcinoma
• resectability

• Humans
• Neoadjuvant Therapy/methods
• Pancreatic Neoplasms/therapy
• Carcinoma, Pancreatic Ductal/therapy
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Fluorouracil/therapeutic use
• Fluorouracil/administration & dosage
• Oxaliplatin/therapeutic use
• Oxaliplatin/administration & dosage
• Pancreatectomy/methods
• Irinotecan
• Leucovorin

• Humans
• Retrospective Studies
• Neoadjuvant Therapy
• Neoplasm Recurrence, Local/pathology
• Chemoradiotherapy
• Rectal Neoplasms
• Prognosis
• Disease-Free Survival
• Mucins/analysis
• Neoplasm Staging
• Treatment Outcome

• cell-free DNA
• genomic sequencing
• multi-omics
• neoadjuvant chemotherapy
• prognosis
• rectal cancer

The prognostic impact of anastomotic leakage (AL) in rectal cancer remains uncertain. We investigated the prognostic significance of AL in rectal cancer patients who underwent curative surgery, especially in terms of chemoradiotherapy.

A total of 1,818 rectal cancer patients who underwent radical surgery from 2011 to 2015 were retrospectively evaluated. We categorized patients according to AL and compared survival outcomes between the groups before and after matching. In locally advanced rectal cancer patients, we classified patients according to neoadjuvant chemoradiotherapy (nCRT) or adjuvant chemotherapy (aCTx) and analyzed survival outcomes according to AL in each group.

Before matching, overall survival (OS) was significantly worse in the AL (+) group compared to the AL (–) group (P = 0.004). In matched patients, there were no differences in disease-free survival (DFS) and OS between groups (P = 0.423 and P = 0.083, respectively). In subgroup analysis for locally advanced rectal cancer, patients were classified as follows: nCRT (+) and aCTx (+) group; nCRT (+) and aCTx (–) group; nCRT (–) and aCTx (+) group; and nCRT (–) and aCTx (–) group. In the nCRT (–) and aCTx (+) group, patients with AL exhibited significantly worse DFS than patients without AL (P = 0.040). In the other 3 groups, there were no differences in DFS according to AL.

In locally advanced rectal cancer, AL had an adverse effect on oncologic outcome in patients receiving aCTx without nCRT but not in patients receiving nCRT.

• Anastomotic leak
• Neoadjuvant therapy
• Prognosis
• Rectal neoplasms

Neoadjuvant chemoradiotherapy (nCRT) and total rectal mesenteric excision are the main standards of treatment for locally advanced rectal cancer (LARC). Lymph node regression grade (LRG) is an indicator of prognosis and response to preoperative nCRT based on postsurgical metastatic lymph node pathology. Common histopathological findings in metastatic lymph nodes after nCRT include necrosis, hemorrhage, nodular fibrosis, foamy histiocytes, cystic cell reactions, areas of hyalinosis, residual cancer cells, and pools of mucin. A number of LRG systems designed to classify the amount of lymph node regression after nCRT is mainly concerned with the relationship between residual cancer cells and regressive fibrosis and with estimating the number of lymph nodes existing with residual cancer cells. LRG offers significant prognostic information, and in most cases, LRG after nCRT correlates with patient outcomes. In this review, we describe the systematic classification of LRG after nCRT, patient prognosis, the correlation with tumor regression grade, and the typical histopathological findings of lymph nodes. This work may serve as a reference to help predict the clinical complete response and determine lymph node regression in patients based on preservation strategies, allowing for the formulation of more accurate treatment strategies for LARC patients, which has important clinical significance and scientific value.

• Lymph node regression grade
• Histopathological
• Rectal cancer
• Chemoradiotherapy
• Treatment response
• Neoadjuvant therapy

• Acellular mucin
• Colon cancer
• Lymph nodes
• Untreated

Neoadjuvant chemoradiotherapy (nCRT) prior to surgery is the standard treatment for patients with locally advanced rectal cancer (LARC), while parts of them show poor therapeutic response accompanied by therapy adverse effects. Predictive biomarkers for nCRT response could facilitate the guidance on treatment decisions but are still insufficient until now, which limits the clinical applications of nCRT in LARC patients.

In our study, 37 formalin-fixed paraffin-embedded tumor biopsies were obtained from patients with LARC before receiving 5-fluorouracil based nCRT. Proteomics analyses were conducted to identify the differentially expressed proteins (DEPs) between total responders (TR) and poor responders (PR). The DEPs were validated via ROC plotter web tool and their predictive performance was evaluated by receiver operating characteristic analysis. Functional enrichment analyses were performed to further explore the potential mechanisms underlying nCRT response.

Among 3,998 total proteins, 91 DEPs between TR and PR were screened out. HSPA4, NIPSNAP1, and SPTB all with areas under the curve (AUC) ~ 0.8 in the internal discovery cohort were independently validated by the external mRNA datasets (AUC ~ 0.7), and their protein levels were linearly correlated with the graded responses to nCRT in the internal cohort. The combination of HSPA4 and SPTB could distinctly discriminate the TR and PR groups (AUC = 0.980, p < 0.0001). Moreover, multiple combinations of the three proteins realized increased specificity and/or sensitivity, while achieving favorable predictive value when moderate responders were introduced into the ROC analysis. Pathways including DNA damage repair, cell cycle, and epithelial mesenchymal transition were involved in nCRT response according to the enrichment analysis results.

HSPA4, SPTB and NIPSNAP1 in tumor biopsies and/or their optional combinations might be potential predictive markers for nCRT response in patients with LARC. The DEPs and their related functions have implications for the potential mechanisms of treatment response to nCRT in patients with LARC.

The online version contains supplementary material available at 10.1186/s12935-022-02530-0.

• Locally advanced rectal cancer
• Neoadjuvant chemoradiotherapy
• Predictive marker
• Proteomics

Organ preservation can enable locally advanced rectal cancer (LARC) patients with clinical complete response (cCR) after neoadjuvant treatment to maintain quality of life. In this study, we aimed to evaluate whether one or two cycles of capecitabine after neoadjuvant chemoradiotherapy (NCRT) without extending the interval between the end of NCRT and surgery could increase the complete response (CR) rate in low-risk middle-low LARC patients.

We retrospectively evaluated middle-low LARC patients with low risk defined as clinical T2-3b, mesorectal fascia-clear, and extramural vascular invasion-negative by magnetic resonance imaging (MRI), treated between January 2015 and July 2019. Patients were divided into two groups according to whether consolidation chemotherapy was administered after NCRT. Patients in the consolidation chemotherapy group received one or two cycles of capecitabine (1000 mg/m² twice daily from days 1 to 14). The main outcome was the CR rate, including pathological CR (pCR) and cCR.

A total of 169 patients, 105 in the consolidation chemotherapy group and 64 in the non-consolidation chemotherapy group, were included in the study, and the median follow-up was 37.2 months (range, 0.4–71.2 months). Seventeen patients achieved cCR and the remaining 152 underwent surgery after neoadjuvant treatment. There was no significant difference in the CR rate (39.0% vs. 35.9%, p=0.686), ypT0-2N0 rate (65.2% vs. 63.3%, p=0.812), or ypN0 rate (83.7% vs. 88.3%, p=0.503) between the consolidation chemotherapy and non-consolidation chemotherapy groups. Among the patients achieved cCR, 3 (17.6%) experienced regrowth in the rectum and 2 (11.8%) experienced distant metastasis. There was also no significant difference in the 3-year disease-free survival (87.4% vs 85.9%, p=0.971) in patients who underwent surgery between the two groups. Multivariate logistic regression analysis indicated that normal Carcinoma Embryonic Antigen (CEA) levels (p = 0.001) were associated with a higher CR rate. Moreover, there were no significant differences in the incidences of grade ≥2 acute toxicities during neoadjuvant treatment.

Although there was no increase in treatment-related toxicities between the two groups, simply adding one or two cycles of capecitabine after NCRT might be insufficient to benefit low-risk middle-low LARC patients.

• capecitabine
• complete response
• consolidation chemotherapy
• low-risk rectal cancer
• neoadjuvant chemoradiotherapy

• Neoadjuvant therapy
• Pathologic complete response
• Rectal cancer
• Tumor regression grade

• Chemoradiotherapy
• Cross-Sectional Studies
• Humans
• Neoadjuvant Therapy
• Neoplasm Staging
• Rectal Neoplasms/diagnostic imaging
• Rectal Neoplasms/surgery
• Rectum/pathology
• Treatment Outcome

• Università degli Studi di Trieste

• locally advanced rectal cancer
• neoadjuvant chemoradiotherapy
• neutrophil-to-lymphocyte ratio
• pathological complete response
• prognostic factor

• MOST 109-2314-B-037-035, MOST 109-2314-B-037-040, MOST 109-2314-B-037-046-MY3, MOST110-2314-B-037-097 Ministry of Science and Technology, Taiwan
• MOHW109-TDU-B-212-134026, MOHW109-TDU-B-212-114006, MOHW110-TDU-B-212-1140026 Ministry of Health and Welfare

• Apoptosis
• CRT
• Pathological response
• Tumor regression grade

• apoptosis
• chemo-resistance
• colorectal
• mucin

• FOLFIRINOX
• Neoadjuvant chemotherapy
• Neoadjuvant therapy
• Pancreatic cancer
• Precision medicine

• acellular mucin pools
• chemoradiotherapy
• pathological complete response
• prognosis
• rectal cancer

• Sun Yat-sen University Clinical Research 5010 Program
• Natural Science Foundation of Guangdong Province
• Medical Scientific Research Foundation of Guangdong Province
• National Natural Science Foundation of China

• Local advanced rectal cancer
• preoperative chemoradiotherapy
• prognosis
• pulmonary metastasis
• risk factors

Thanks to the development of modern chemotherapeutic regimens, survival after surgery for pancreatic ductal adenocarcinoma (PDAC) has improved and pancreatologists worldwide agree that the treatment of PDAC demands a multidisciplinary approach. Neoadjuvant treatment (NAT) plays a major role in the treatment of PDAC since only about 20% of patients are considered resectable at the time of diagnosis. Moreover, increasing data demonstrating the benefits of NAT for borderline resectable/locally advanced PDAC are driving a shift from up-front surgery to NAT in the multidisciplinary treatment of even resectable PDAC. Our understanding of the role of NAT in PDAC has evolved from tumor shrinkage to controlling potential micrometastases and selecting patients who may benefit from radical resection. The present review gives an overview on the current literature of NAT concepts for BR/LA PDAC and resectable PDAC.

• FOLFIRINOX
• borderline resectable
• gemcitabine
• locally advanced
• nab-paclitaxel
• neoadjuvant chemoradiotherapy
• neoadjuvant chemotherapy
• neoadjuvant therapy

• Carcinoembryonic antigens
• Chemoradiotherapy
• Radiologic response
• Rectal cancer

• colorectal cancer
• diffuse reflectance spectroscopy
• fibrosis
• machine learning
• tumor

• Colorectal neoplasms
• Pathology report
• Protocol
• Standardization

• Computed tomography
• Magnetic resonance imaging
• Mucin
• Positron emission tomography
• Rectal neoplasms

• Computed tomography
• Magnetic resonance imaging
• Mucin
• Positron emission tomography
• Rectal neoplasms

• Adenocarcinoma, Mucinous/diagnostic imaging
• Adenocarcinoma, Mucinous/pathology
• Adenocarcinoma, Mucinous/therapy
• Chemoradiotherapy
• Humans
• Neoadjuvant Therapy
• Neoplasm Staging
• Rectal Neoplasms/diagnostic imaging
• Rectal Neoplasms/pathology
• Rectal Neoplasms/therapy

• P30 CA008748 NCI NIH HHS

• Chemoradiotherapy
• Metastasis
• Pathological complete response
• Prognosis
• Rectal cancer

• mucin pools
• neoadjuvant treatment
• radiotherapy
• rectal cancer
• response

• laparoscopic surgery
• magnetic resonance imaging
• pelvimetry
• rectal cancer
• total mesorectal excision

The aim of this retrospective study was to compare volumetric-modulated arc therapy using simultaneous integrated boosts (SIB-VMAT) of 45 Gy/55 Gy in 25 fractions with three-dimensional conformal radiotherapy (3D–CRT) in preoperative chemoradiation for rectal cancers.

In the propensity score-matching analysis of 1:2, we selected 60 patients from the SIB-VMAT group and 120patients from the 3D–CRT group matched pairings out of 145 patients between 2005 and 2015. The regimen of concurrent combined chemotherapy was oral uracil/tegafur plus leucovorin with/without irinotecan.

There were no significant differences between the two groups, in pathological complete response rates (pCR) (11% in the 3D–CRT group vs. 17% in the SIB-VMAT group, P = 0.39), pathological response rates (44% vs. 60%, P = 0.77), disease-free survival (P = 0.32), or local control (P = 0.52). The SIB-VMAT method marginally improved the rate of pathological grade 2–3 effects and the OS was significantly better in patients with grade 2–3 effects. Recurrence was seen in 36 patients (30%) in the 3D–CRT group and 19 patients (32%) in the SIB-VMAT group. The first distant recurrence site in the SIB-VMAT group was liver in 6 patients and lung in 8 patients. The obvious radiation-induced late toxicity in the SIB-VMAT group was recto-vesical fistula in two patients.

The SIB-VMAT may be a promising method for preoperative CRT of rectal cancer.

• Image-guided radiotherapy
• Intensity-modulated radiotherapy
• Preoperative radiotherapy
• Rectal cancer
• Simultaneous integrated boost

The aim of the study was to evaluate the added value of the apparent diffusion coefficient (ADC) of diffusion-weighted magnetic resonance imaging (DW-MRI) in patients with rectal cancer who received neoadjuvant chemoradiotherapy (CRT). The use of DW-MRI for response evaluation in rectal cancer still remains a widely investigated issue, as the accurate detection of pathologic complete response (pCR) is critical in making therapeutic decisions.

Thirty-three patients with locally advanced rectal cancer were evaluated retrospectively by MRI in addition to diffusion-weighted images (DWI) and its ADC pre- and post-neoadjuvant CRT. These patients subsequently underwent curative-intent surgery. Tumor staging by MRI and ADC value were compared with histopathological findings of the surgical specimen.

MRI in addition to DWI had a sensitivity of 96.1%, specificity of 71.4%, positive predictive value of 92.5%, and negative predictive value of 83.3% in the detection of pCR. The pre-CRT ADC alone could not reliably predict the pCR group. Post-CRT ADC cutoff value of 1.49 x 10⁻³ mm²/s had the highest accuracy and allowed a 16.7% increase in negative predictive value and 3.9% increase in sensitivity. Patients with pCR to neoadjuvant treatment differed from the other groups in their absolute values of post-CRT ADC (p < 0.01).

The use of post-CRT ADC increased the diagnostic performance of MRI in addition to DWI in predicting the final pathologic staging of rectal carcinoma.

• diffusion MRI
• neoadjuvant therapy
• rectal cancer

• Chemoradiotherapy
• Neoadjuvant therapy
• Rectal cancer
• Recurrence

The standard of care in locally advanced rectal cancer is neoadjuvant chemoradiation (nCRT) followed by radical surgery. Response to nCRT varies among patients and pathological complete response is associated with better outcome. However, there is a lack of effective methods to select rectal cancer patients who would or would not have a benefit from nCRT. The utility of clinicopathological and radiological features are limited due to lack of adequate sensitivity and specificity. Molecular biomarkers have the potential to predict response to nCRT at an early time point, but none have currently reached the clinic. Integration of diverse types of biomarkers including clinicopathological and imaging features, identification of mechanistic link to tumor biology, and rigorous validation using samples which represent disease heterogeneity, will allow to develop a sensitive and cost-effective molecular biomarker panel for precision medicine in rectal cancer. Here, we aim to review the recent advance in tissue- and blood-based molecular biomarker research and illustrate their potential in predicting nCRT response in rectal cancer.

• biomarker
• neoadjuvant chemoradiation
• rectal cancer

• Biomarkers
• Chemoradiotherapy
• DNA Methylation
• DNA, Neoplasm
• Gene Expression Profiling
• Humans
• Metabolomics/methods
• MicroRNAs
• Mutation
• Neoadjuvant Therapy
• Polymorphism, Single Nucleotide
• Prognosis
• Proteome
• Proteomics/methods
• Rectal Neoplasms/diagnosis
• Rectal Neoplasms/genetics
• Rectal Neoplasms/metabolism
• Rectal Neoplasms/therapy
• Transcriptome
• Tumor Microenvironment

To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and surgery.

Tumor regression grade (TRG) according to the Dworak system and yTNM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced (cTNM stage II and III) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival (DFS) and cancer specific survival (CSS) was analyzed by Kaplan Meier and Cox-regression analyses.

cN+ status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response (low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified two-tiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The two-tiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic variables.

Our data suggest that caution should be applied in using a conservative approach in rectal carcinomas with cN+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma.

• Rectal carcinoma
• Dworak
• Acellular mucin pools
• Downstaging
• Mucinous

• Adenocarcinoma/diagnosis
• Adenocarcinoma/therapy
• Adult
• Aged
• Aged, 80 and over
• Biopsy
• Cell Differentiation
• Chemoradiotherapy/methods
• Disease-Free Survival
• Female
• Humans
• Italy
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Prognosis
• Proportional Hazards Models
• Rectal Neoplasms/diagnosis
• Rectal Neoplasms/therapy
• Registries
• Retrospective Studies
• Treatment Outcome

• Laparoscopic total mesorectal excision
• Locally advanced rectal cancer
• Neoadjuvant chemoradiation therapy
• Surgical morbidity
• Tumor regression grading

• peritoneal matastasis
• peritoneal regression grading score
• regresion

• Cellular mucin
• Neoadjuvant chemoradiation
• Outcome
• Pathological response
• Rectal cancer

• Cell Differentiation
• Chemoradiotherapy
• Humans
• Inflammation
• Lymph Nodes/pathology
• Mucins/metabolism
• Neoadjuvant Therapy
• Neoplasm Staging
• Prognosis
• Rectal Neoplasms/diagnosis
• Rectal Neoplasms/drug therapy
• Rectal Neoplasms/radiotherapy
• Treatment Outcome

• Adenocarcinoma/pathology
• Adenocarcinoma/secondary
• Adenocarcinoma/therapy
• Chemoembolization, Therapeutic/methods
• Disease-Free Survival
• Hepatic Artery
• Humans
• Liver Neoplasms/pathology
• Liver Neoplasms/secondary
• Liver Neoplasms/therapy
• Male
• Middle Aged
• Rectal Neoplasms/pathology
• Remission Induction
• Time Factors

Rectal adenocarcinoma is an important cause of cancer-related deaths worldwide, and key anatomic differences between the rectum and the colon have significant implications for management of rectal cancer. Many advances have been made in the diagnosis and management of rectal cancer. These include clinical staging with imaging studies such as endorectal ultrasound and pelvic magnetic resonance imaging, operative approaches such as transanal endoscopic microsurgery and laparoscopic and robotic assisted proctectomy, as well as refined neoadjuvant and adjuvant therapies. For stage II and III rectal cancers, combined chemoradiotherapy offers the lowest rates of local and distant relapse, and is delivered neoadjuvantly to improve tolerability and optimize surgical outcomes, particularly when sphincter-sparing surgery is an endpoint. The goal in rectal cancer treatment is to optimize disease-free and overall survival while minimizing the risk of local recurrence and toxicity from both radiation and systemic therapy. Optimal patient outcomes depend on multidisciplinary involvement for tailored therapy. The successful management of rectal cancer requires a multidisciplinary approach, with the involvement of enterostomal nurses, gastroenterologists, medical and radiation oncologists, radiologists, pathologists and surgeons. The identification of patients who are candidates for combined modality treatment is particularly useful to optimize outcomes. This article provides an overview of the diagnosis, staging and multimodal therapy of patients with rectal cancer for primary care providers.

• Rectal cancer
• Diagnosis
• Treatment
• Review
• Primary care

• Adenocarcinoma/diagnosis
• Adenocarcinoma/mortality
• Adenocarcinoma/therapy
• Combined Modality Therapy
• Evidence-Based Medicine
• Humans
• Patient Selection
• Predictive Value of Tests
• Primary Health Care
• Rectal Neoplasms/diagnosis
• Rectal Neoplasms/mortality
• Rectal Neoplasms/therapy
• Risk Factors
• Treatment Outcome

• Chemoradiotherapy, Adjuvant
• Combined Modality Therapy
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multivariate Analysis
• Neoadjuvant Therapy
• Neoplasm Metastasis
• Neoplasm Recurrence, Local
• Neoplasm Staging
• Preoperative Period
• Prognosis
• Rectal Neoplasms/pathology
• Rectal Neoplasms/surgery
• Rectal Neoplasms/therapy
• Retrospective Studies
• Time Factors
• Treatment Outcome