Genomic evolution during locoregional recurrence in colorectal cancer determined by whole-exome sequencing: a retrospective observational study

Objective:The genomic landscapes of metastatic colorectal cancer(mCRC)have been extensively studied;however,the genetic mechanisms underlying the locoregional recurrence(LR)of CRC remain unclear.The objective of our study was to investigate genomic evolution during LR in CRC using high-throughput sequencing.Methods:Twenty-three CRC patients with matched primary and LR tissues were recruited from Nanfang Hospital and Zhejiang Cancer Hospital between January 2011 and December 2018.The last date of follow-up was March 2020.Tissue samples were analyzed by whole-exome sequencing and the genomic profiles were depicted by single nucleotide variation,mutational signature,copy number variation,clonal architecture,and other features.The evolutionary process was speculated with comparison of the genetic variations between primary and LR lesions.The disseminating clusters from primary to LR lesions were identified by variant allele frequency dynamics.Furthermore,the early-recurrent biomarker was explored by comparing the indel signature between early-and late-recurrent patients.The study was approved by the Institutional Review Board of Nanfang Hospital of Southern Medical University(approval No.2020010)on September 11,2020.Results:The results highlighted distinct origins of LR between patients with high microsatellite instability and microsatellite stability.LR lesions evolved independently in patients with high microsatellite instability,while LR lesions were highly clonally related to the primary lesions in patients with microsatellite stability.Late-acquired variations in LR lesions encompassed a wide range of driver genes involved in histone methylation,DNA replication,T cell activation,PDCD1 gain,and LMNA loss.Furthermore,clonal analysis of the disseminating cells identified a dominant polyclonal seeding pattern during LR.The indel signature ID4 was associated with significantly shorter disease-free survival in patients with relapsed CRC according to a public dataset.Conclusion:These findings pose a challenge for the development of new approaches targeting the interactions of multiple clones in the establishment of LR and in terms of optimizing the clinical management of susceptible patients.

Selective lateral lymph node dissection after neoadjuvant chemoradiotherapy in rectal cancer

BACKGROUND Lateral lymph node metastasis is one of the leading causes of local recurrence in patients with advanced mid or low rectal cancer.Neoadjuvant chemoradiotherapy(NCRT)can effectively reduce the postoperative recurrence rate;thus,NCRT with total mesorectal excision(TME)is the most widely accepted standard of care for rectal cancer.The addition of lateral lymph node dissection(LLND)after NCRT remains a controversial topic.AIM To investigate the surgical outcomes of TME plus LLND,and the possible risk factors for lateral lymph node metastasis after NCRT.METHODS This retrospective study reviewed 89 consecutive patients with clinical stage II-III mid or low rectal cancer who underwent TME and LLND from June 2016 to October 2018.In the NCRT group,TME plus LLND was performed in patients with short axis(SA)of the lateral lymph node greater than 5 mm.In the non-NCRT group,TME plus LLND was performed in patients with SA of the lateral lymph node greater than 10 mm.Data regarding patient demographics,clinical workup,surgical procedure,complications,and outcomes were collected.Multivariate logistic regression analysis was performed to evaluate the possible risk factors for lateral lymph node metastasis in NCRT patients.RESULTS LLN metastasis was pathologically confirmed in 35 patients(39.3%):26(41.3%)in the NCRT group and 9(34.6%)in the non-NCRT group.The most common site of metastasis was around the obturator nerve(21/35)followed by the internal iliac artery region(12/35).In the NCRT patients,46%of patients with SA of LLN greater than 7 mm were positive.The postoperative 30-d mortality rate was 0%.Two(2.2%)patients suffered from lateral local recurrence in the 2-year follow up.Multivariate analysis showed that cT4 stage(odds ratio[OR]=5.124,95%confidence interval[CI]:1.419-18.508;P=0.013),poor differentiation type(OR=4.014,95%CI:1.038-15.520;P=0.044),and SA≥7 mm(OR=7.539,95%CI:1.487-38.214;P=0.015)were statistically significant risk factors associated with LLN metastasis.CONCLUSION NCRT is not sufficient as a stand-alone therapy to eradicate LLN metastasis in lower rectal cancer patients and surgeons should consider performing selective LLND in patients with greater LLN SA diameter,poorer histological differentiation,or advanced T stage.Selective LLND for NCRT patients can have a favorable oncological outcome.

Review of clinical investigation on recurrence of gastric cancer following curative resection

Objective To discuss the present status and progress of clinical research on recurrence of gastric cancer after surgery, including patterns, clinicopathologic factors, prognosis, detection, diagnosis, prevention, and treatment strategies. Data sources The data used in this review were mainly from PubMed articles published in English from 2000 to August 2011. The search terms were ＂gastric cancer＂ and ＂recurrence＂. Study selection Articles were selected if they involved clinicopathologic factors, detection methods, and treatment strategies of recurrence of gastric cancer. Results Peritoneal recurrence is the most common pattern in recurrence of gastric cancer. The main risk factors for recurrence of gastric cancer are tumor stage, including depth of tumor invasion and lymph node metastasis, and Borrmann classification. The prognosis of patients with recurrence is very poor, especially patients with peritoneal recurrence. Systemic chemotherapy is still the main treatment method for patients with recurrent cancer. If complete resection can be accomplished, some benefits may be obtained from surgery for recurrence. However, standard treatment for patients with recurrence has not yet been established. Conclusions Early detection and diagnosis of recurrence is quite crucial for treatment and prognosis. The optimal therapeutic strategy for recurrence should be based on a multidisciplinary assessment and the patient＇s individual state and should involve combined therapy.

Axillary recurrence after intramammary sentinel lymph nodes metastases with capsular extravasation

Axillary recurrence is a rare event in patients treated with sentinel lymph node biopsy alone with the majority occurring in the first 5 years after surgery. Intramammary lymph node (IMLN) can be the primary sites of metastasis and sentinel lymph nodes, but the clinical significance, including prognosis and therapeutic approach is yet unclear, even more with capsular extravasation. IMLN metastases are strongly correlated with axillary lymph nodes involvement and therefore a guide for further surgical management of the axillary nodes.

Age exerts a continuous effect in the outcomes of Asian breast cancer patients treated with breast-conserving therapy

Background:Asians are diagnosed with breast cancer at a younger age than Caucasians are.We studied the effect of age on locoregional recurrence and the survival of Asian breast cancer patients treated with breast-conserving therapy.Methods:Medical records of 2492 patients treated with breast-conserving therapy between 1989 and 2012 were reviewed.The Kaplan-Meier method was used to estimate locoregional recurrence,breast cancer-free survival,and breast cancer-specific survival rates.These rates were then compared using log-rank tests.Outcomes and age were modeled by Cox proportional hazards.Fractional polynomials were then used to test for non-linear relationships between age and outcomes.Results:Patients≤40 years old were more likely to have locoregional recurrence than were older patients(Hazard ratio[HR]=2.32,P<0.001).Locoregional recurrence rates decreased year-on-year by 4%for patients with luminal-type breast cancers,compared with 8%for those with triple-negative cancers.Similarly,breast cancer-free survival rates increased year-on-year by 4%versus 8%for luminal-type and triple-negative cancers,respectively.Breast cancer-spe-cific survival rates increased with age by 5%year-on-year.Both breast cancer-free survival and breast cancer-specific survival rates in patients with luminal cancers exhibited a non-linear(“L-shaped”)relationship-where decreasing age at presentation was associated with escalating risks of relapse and death.The influence of age on overall survival was confounded by competing non-cancer deaths in older women,resulting in a“U-shaped”relationship.Conclusions:Young Asian breast cancer patients have a continuous year-on-year increase in rates of disease relapse and cancer deaths compared with older patients with no apparent threshold.