5-year Disease-free Survival Rates Research Articles

Local excision for middle-low rectal cancer after neoadjuvant chemoradiation: A retrospective study from a single tertiary center

BACKGROUND Rectal cancer has become one of the leading malignancies threatening people’s health. For locally advanced rectal cancer (LARC), the comprehensive strategy combining neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant chemotherapy has emerged as a standard treatment regimen, leading to favorable local control and long-term survival. However, in recent years, an increasing attention has been paid on the exploration of organ preservation strategies, aiming to enhance quality of life while maintaining optimal oncological treatment outcomes. Local excision (LE), compared with low anterior resection (LAR) or abdominal-perineal resection (APR) was introduced dating back to 1970’s. LE has historically been linked to a heightened risk of recurrence compared to TME, potentially due to occult lymph node metastasis and intraluminal recurrence. Recent evidence has demonstrated that LE might be an alternative approach, instead of LAR or APR, in cases with favorable tumor regression after NCRT with potentially better quality of life. Therefore, a retrospective analysis of clinicopathological data from mid-low LARC patients who underwent LE after NCRT was conducted, aiming to evaluate the treatment's efficacy, safety, and oncologic prognosis. AIM To explore the safety, efficacy, and long-term prognosis of LE in patients with mid-low rectal cancer who had a good response to NCRT. METHODS Patients with LE between 2012 to 2021 were retrospectively collected from the rectal cancer database from Gastro-intestinal Ward III in Peking University Cancer Hospital. The clinicopathological features, postoperative complications, and long-term prognosis of these patients were analyzed. The Kaplan-Meier method was used to create cancer-specific survival curve, and the log-rank test was used to compare the differences regarding outcomes. RESULTS A total of 33 patients were included in this study. The median interval between NCRT and surgery was 25.4 (range: 8.7-164.4) weeks. The median operation time was 57 (20.0-137.0) minutes. The initial clinical T staging (cT): 9 (27.3%) patients were cT2, 19 (57.6%) patients were cT3, and 5 (15.2%) patients were cT4; The initial N staging (cN): 8 patients (24.2%) were cN negative, 25 patients (75.8%) were cN positive; The initial M stage (cM): 2 patients (6.1%) had distant metastasis (ycM1), 31 (93.9%) patients had no distant metastasis (cM0). The pathological results: 18 (54.5%) patients were pathological T0 stage (ypT0), 6 (18.2%) patients were ypT1, 7 (21.2%) patients were ypT2, and 2 (6.1%) patients were ypT3. For 9 cT2 patients, 5 (5/9, 55.6%) had a postoperative pathological result of ypT0. For 19 cT3 patients, 11 (57.9%) patients were ypT0, and 2 (40%) were ypT0 in 5 cT4 patients. The most common complication was chronic perineal pain (71.4%, 5/7), followed by bleeding (43%, 3/7), stenosis (14.3%, 1/7), and fecal incontinence (14.3%, 1/7). The median follow-up time was 42.0 (4.0-93.5) months. For 31 patients with cM0, the 5-year disease-free survival (DFS) rate, 5-year local recurrence-free survival (LRFS) rate, and 5-year overall survival (OS) rate were 88.4%, 96.7%, and 92.9%, respectively. There were significant differences between the ycT groups concerning either DFS (P = 0.042) or OS (P = 0.002) in the Kaplan-Meier analysis. The LRFS curve of ycT ≤ T1 patients was better than that of ycT ≥ T2 patients, and the P value was very close to 0.05 (P = 0.070). The DFS curve of patients with ypT ≤ T1 was better than that of patients with ypT ≥ T2, but the P value was not statistically significant (P = 0.560). There was a significant difference between the ypT groups concerning OS (P = 0.014) in the Kaplan-Meier analysis. The LRFS curve of ypT ≤ T1 patients was better than that of ypT ≥ T2 patients, and the P value was very close to 0.05 (P = 0.070). Two patients with initial cM1 were alive at the last follow-up. CONCLUSION LE for rectal cancer with significant tumor regression after NCRT can obtain better safety, efficiency, and oncological outcome. Minimally invasive or nonsurgical treatment with patient participation in decision-making can be performed for highly selected patients. Further investigation from multiple centers will bring better understanding of potential advantages regarding local resection.

Prognostic value of preoperative D-dimer to albumin ratio in patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy

BackgroundThe prognostic value of Albumin and D-dimer has been established for multiple tumor types, indicating their potential for predicting tumor development. Nevertheless, the predictive capability of the DDI-to-albumin ratio (DAR) in locally advanced rectal cancer (LARC) remains uncertain.PurposeThe objective of this study was to investigate the prognostic significance of the DAR in LARC.MethodsA total of 513 patients who underwent neoadjuvant chemoradiotherapy (nCRT) prior to total mesorectal excision (TME) between March 2013 to October 2019 were included in this study. Patients were divided into high-level DAR (> 0.016) or low-level DAR (≤ 0.016) groups based on ROC curve analysis optimum cut-off value. The prognostic value of the DAR in LARC was analyzed.ResultsThe study enrolled 513 patients. Patients were stratified into high-level DAR (> 0.016) and low-level DAR (≤ 0.016) cohorts according to the optimal cut-off value determined by ROC curve analysis. The 5-year overall survival (OS) rates for patients in the low DAR group (≤ 0.016) and the high DAR group (> 0.016) were 89.4% and 80.9%, respectively (p = 0.013). The 5-year disease-free survival (DFS) rates were 85.7% and 77.4% (p = 0.027). Multivariate analyses demonstrated that DAR were independent prognostic factors for OS (p = 0.02) and DFS (0.025). Predictive nomograms that included the DAR score group (C-index: OS-0.743, DFS-0.705) were superior to those without DAR scores (C-index: OS-0.721, DFS-0.697).ConclusionThe DAR demonstrates high usability and prognostic value in predicting OS and DFS outcomes among patients diagnosed with LARC who undergo nCRT.

Adjuvant Immunotherapy Does Not Improve Survival in Non-small Cell Lung Cancer with Major/Complete Pathological Response after Induction Immunotherapy

In patients with resectable non-small cell lung cancer (NSCLC), immune checkpoint inhibitor (ICI)-based regimens in both neoadjuvant and perioperative settings demonstrate survival benefit. To date, no study has compared the efficacy between pure neoadjuvant and perioperative approaches, especially in patients who achieve substantial pathological responses. In this retrospective study, patients with clinical stage II-IIIB NSCLC who achieved either major (MPR) or complete (pCR) pathological response after induction ICI plus chemotherapy followed by resection between 2019 and 2023 were identified from multicenter databases. Inverse probability of treatment weighting-adjusted Cox regression was performed to compare disease-free survival (DFS) and overall survival (OS) between patients who did and did not receive ICIs postoperatively. One hundred thirty-six patients who achieved pCR and seventy-two patients who achieved MPR were enrolled. Three-quarters of them had squamous cell cancer. The inverse probability-weighted cohort represented 208 weighted patient cases (adjuvant ICI, 117; control, 91). The weighted DFS/OS rates did not differ between the adjuvant-ICI group and the control group (3-year DFS rates: 90.2% vs. 93.2%, hazard ratio [HR]= 2.47, 95% confidence interval [CI]: 0.74 to 8.22; 3-year OS rates: 89.1% vs. 93.9%, HR=2.44, 95% CI: 0.71 to 8.34). Adverse events during the postoperative ICI treatment were found in 19 of 120 patients (15.8%) and led to adjuvant ICI termination in 18 patients (15.0%). Adjuvant ICI does not improve survival in NSCLC patients who achieve pCR/MPR following neoadjuvant immunochemotherapy. A de-escalation strategy could be considered given the adverse events associated with postoperative ICI treatment.

Phase 2, Multicenter, Open-label, Nonrandomized Study of Neoadjuvant Chemotherapy Liposomal Irinotecan With 5-Fluorouracil, Leucovorin, and Oxaliplatin, Followed by Chemoradiotherapy in Patients With Rectal Cancer in a Watch-and-Wait Program.

To evaluate the efficacy of neoadjuvant chemotherapy combination with liposomal irinotecan, 5-fluorouracil, leucovorin, and oxaliplatin in patients with locally advanced rectal cancer. This was a phase 2, nonrandomized, multicenter study in adults with stage II or III rectal cancer and an Eastern Cooperative Oncology Group performance status of 0 to 1. Total neoadjuvant therapy (TNT) consisted of neoadjuvant chemotherapy combination with liposomal irinotecan (60mg/m2), oxaliplatin (60mg/m2), leucovorin (400mg/m2), and fluorouracil (2400mg/m²), followed by chemoradiotherapy [ie, capecitabine (825mg/m2) and radiotherapy according to the standard of care]. The primary efficacy endpoint was the proportion of patients who achieved clinical complete response (cCR), defined as the normalization of pelvic magnetic resonance imaging, rectoscopy, computed tomography scan, and tumor markers. The median follow-up was 32.3 months. Of the 30 patients who underwent TNT and were evaluated, 6 (20.0%; 95% CI: 5.2%-34.8%) patients achieved a cCR. There were no deaths. The median disease-free survival (DFS) for patients with cCR was not reached after a follow-up of 32 months; the 1-year DFS rate was 90.0% (95% CI: 71.0%-100%), and the 2-year and 3-year DFS rates were 80.0% (95% CI: 55.0%-100%). No grade ≥4 adverse events (AEs) were observed. Grade 3 AEs occurred in 18 patients (60%), most frequent was diarrhea (n = 9, 30%). Eleven (36.7%) patients experienced serious AEs, with diarrhea being the most frequent (n = 6, 20.0%). TNT with 5-fluorouracil, leucovorin, and oxaliplatin and chemoradiation is a safe and effective therapeutic alternative for the management of locally advanced rectal cancer.

Comparison of efficacy and safety of neoadjuvant immunochemotherapy in young and elderly patients with IIA–IIIB non-small-cell lung cancer in real-world practice

ObjectiveThere is currently no consensus over whether neoadjuvant immunochemotherapy is more effective in young patients than in elderly patients with IIA–IIIB non-small-cell lung cancer (NSCLC). In this study, we compare the efficacy and safety of neoadjuvant immunochemotherapy in young and elderly patients with IIA–IIIB NSCLC.MethodsThis retrospective study consecutively included IIA–IIIB NSCLC patients who received 2–4 cycles preoperative immunochemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine from 2019 to 2022. The 1:1 propensity score match analysis was conducted to balance the confounding factors between the young patient group (< 65 years old) and elderly patient group (≥ 65 years old). The follow-up period would not end until at least 1 year after surgery or patient’s decision to abandon treatment. The primary endpoint was pathological response, while the secondary endpoints were objective response rate (ORR), adverse events (AEs), disease-free survival (DFS) and overall survival (OS).ResultsA total of 179 patients were included in our study: <65 years group (71 patients) and ≥ 65 years group (108 patients). After a 1:1 propensity score matching,132 patients (66 pairs) were analyzed to compare the efficacy and safety between the two groups. The ORR in the young patient group and elderly patient group was 72.7% and 71.2% (P = 1.000), respectively. The incidence of grade 3–4 AEs in the elderly patient group was similar to the young patient group (13.6% vs. 16.7%, P = 0.627). About 62.1% (41/66) in the young patient group and 54.5% (36/66) in the elderly patient group eventually underwent surgery. The rate of major pathological response (MPR) in the young patient group and elderly patient group was 68.3% and 55.6% (P = 0.903), respectively. The rate of pathological complete response (pCR) in the young patient group was significantly higher than that in the elderly patient group (46.3% vs. 22.2%, P = 0.027). The median DFS in the young patient group was not reached and 32.2 months in the elderly patient group (P = 0.071). The 1-year DFS rate, 2-year DFS rate and 3-year DFS rate in the young patient group were 90.2%, 85.4% and 80.5%, with that in the elderly patient group 86.1%, 69.4% and 66.7%. The median OS in the young patient group was 42.4 months and not reached in the elderly patient group (P = 0.067). The 1-year OS rate, 2-year OS rate and 3-year OS rate in the young patient group were 97.6%, 90.2% and 90.2%, with that in the elderly patient group 88.9%, 80.6% and 72.2%.ConclusionsFor IIA–IIIB NSCLC, neoadjuvant immunochemotherapy in young patients can produce a higher percentage of patients with a pCR than in elderly patients. However, the survival benefits and incidence of AEs are similar in young and elderly patients.

Clinical outcomes of microwave ablation for solitary T1N0M0 papillary thyroid carcinoma: a more than 5-year follow-up study.

This study aimed to evaluate the long-term efficacy and safety of microwave ablation (MWA) for solitary T1N0M0 papillary thyroid carcinoma (PTC) and compare them between T1a and T1b disease. This retrospective study included 136 patients with solitary T1N0M0 PTC who were treated with MWA and followed up for more than 5 years. Outcomes were compared between patients with T1a and T1b disease. The primary outcomes were disease progression and disease-free survival (DFS). The secondary outcomes included the volume reduction rate (VRR), the rate of complete disappearance, and complications. During a mean follow-up period of 70.6 ± 10.5 months, the overall disease progression rate was 5.88%. The incidences of lymph node metastases (LNMs) and new tumors were 2.21% and 5.15%, respectively. No patient was diagnosed with local recurrence, distant metastasis, or death due to PTC. There were no significant differences between the T1a and T1b groups in terms of disease progression (3.81% vs 12.90%, p = 0.15), LNMs (1.90% vs 3.23%, p = 0.54), or new tumors (2.86% vs 12.90%, p = 0.08). The 5-year DFS rate was 94.85%, the VRR was 99.7% ± 2.0%, and 97.79% of the tumors disappeared. Hoarseness occurred in five patients (3.68%). MWA is a long-term effective and safe option for patients with solitary T1N0M0 PTC, providing a minimally invasive alternative for those who refuse surgery or active surveillance. Question MWA, as a minimally invasive alternative for treating PTC, lacks comparison with surgical resection and active surveillance. Findings MWA resulted in overall disease progression in 5.88% of patients with solitary T1N0M0 PTC over more than 5 years of follow-up. Clinical relevance MWA is a safe, effective, and minimally invasive treatment for solitary T1N0M0 PTC, with high DFS rates and low complication rates, benefiting patients seeking alternatives to surgery or active surveillance.

Prognosis and its influencing factors in patients with non-gastric gastrointestinal stromal tumors at low risk of recurrence: a retrospective multicenter study in China

Objective: To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence. Methods: This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16-93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02. Results: With a median follow-up of 63 (12-267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670-0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624-0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion: The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemo-immunotherapy for locally advanced esophageal squamous cell carcinoma

Objective: To compare the clinical efficacy of neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemo-immunotherapy (nCIT) for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Clinical data of patients who received nCRT or nCIT followed by esophagectomy for locally advanced ESCC between January 2010 and December 2022 were retrospectively collected from Zhejiang Cancer Hospital, with 155 patients in the nCRT group and 470 patients in the nCIT group. Propensity score matching (PSM) was performed in the two groups. After PSM, 120 patients were allocated to the nCRT group and 192 patients to the nCIT group. The pathological response and disease recurrence were compared between the two groups after PSM. Log rank test were used to compare the survival outcomes before and after PSM. Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors for locally advanced ESCC. Results: After PSM, the R0 resection rate in the nCRT group and the nCIT group was 93.3% (112/120) and 93.8% (180/192), respectively, with no statistical significance (P=0.884). However, the pathological complete response rate in the nCRT group [36.7% (44/120)] was higher than that in the nCIT group [21.4% (41/192), P=0.003]. For patients with R0 resection, the major recurrence pattern was distant metastasis [18.8% (21/112)] in the nCRT group, while the pattern was locoregional recurrence [12.2% (22/180)] in the nCIT group. The 3-year disease-free survival rates were 52.7% and 66.1% (P=0.022) and the 3-year overall survival rates were 59.2% and 75.5% (P=0.002) in the nCRT and nCIT groups, respectively. Multivariate Cox regression analysis also revealed that the neoadjuvant therapy mode was an independent prognostic factor for patients with locally advanced ESCC. Compared with nCRT, nCIT could significantly prolong disease-free survival (HR=0.58, 95% CI: 0.40-0.86) and overall survival (HR=0.53, 95% CI: 0.35-0.79). Conclusion: These results suggest that nCIT could significantly improve disease-free survival rate and overall survival rate over nCRT in locally advanced ESCC, even with lower pathological complete response rate.

Is postoperative radiotherapy effective in patients with completely resected pathologic stage IIIA(N2) non-small cell lung cancer? High-risk populations should consider it

Background and purposeWe aimed to assess the benefits of postoperative radiotherapy (PORT) in completely resected patients with pathologic stage IIIA(N2) non-small cell lung cancer (NSCLC) with a high risk of locoregional recurrence (LRR). Materials and methodsA prospective, randomized trial was conducted starting in July 2016 to explore the optimal timing of PORT in high-LRR-risk patients with completely resected IIIA(N2) NSCLC (NCT02974426). Patients were identified as high-LRR-risk patients via the prognostic index (PI) model and were randomly assigned to PORT-first or PORT-last treatment. To evaluate PORT for high-LRR-risk patients, all patients in this trial constituted the PORT cohort, whereas high-LRR-risk patients without PORT were selected from a retrospective cohort as the non-PORT cohort. Propensity score-matched (PSM) analyses were conducted to compare overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). ResultsBetween 2016 and 2022, 132 patients were included in the trial, with a median follow-up of 49.3 months. The 3-year OS rate was 83.2 %, and the 3-year DFS rate was 35.0 %. Among these patients, 122 patients (92 %) received planned PORT. For 132 intention-to-treat patients, PSM analysis with the non-PORT cohort (n = 307) resulted in 130 matched pairs. The results revealed that PORT improved LRFS (3-year LRFS, 77.6 % vs. 57.3 %; p = 0.00014), DFS (3-year DFS, 35.2 % vs. 28.6 %; p = 0.038), and OS (3-year OS, 83.0 % vs. 60.7 %; p = 0.00017), with no difference in DMFS (p = 0.17). ConclusionPORT could increase local control, DFS, and OS in high-LRR-risk patients with completely resected IIIA(N2) NSCLC. Future research should utilize multidimensional data to pinpoint more precise subgroups benefiting from PORT, with prospective trials validating these findings.

Multidisciplinary tumor boards in oral cavity cancer: survival effect due to balancing guideline adherence and treatment delays.

The purpose of the study was to assess the impact of a pretherapeutic Multidisciplinary Tumor Board (MTB) presentation on the prognosis and treatment outcomes in patients with primary oral cavity carcinoma. This single-center study included 630 patients diagnosed with oral cavity carcinoma treated between 2010 and 2020. The study cohort was divided in a group with and without pretherapeutic MTB presentation. Data on patient demographics, tumor characteristics, treatment and the time to treatment initiation (TTI) were collected retrospectively. Primary findings revealed no significant difference in 3-year survival rate (3-YSR) and 3-year disease-free survival rate (3-YDFSR) for the non-MTB and MTB group. The 3-YSR was 73.1% in the non-MTB group and 67.1% in the MTB group (p = 0.112). The 3-YDFSR was 73.8% in the non-MTB group and 76.5% in the MTB group (p = 0.447). Estimated mean 5-year survival (5-YS) and 5-year disease-free survival in (5-YDFS) did not differ significantly between both groups, across the UICC stages I-IV, as well as for the entire cohort. The TTI was significantly longer in the MTB group (33.5 days, CI: 31.3;35.7) compared to the non-MTB group (20.1 days, CI: 17.9;22.4, p < 0.001). The MTB group adhered more frequently to the national guidelines (68% vs. 79.6%, p < 0.01). The results demonstrate both positive and negative side effects of the MTB presentation in patients with oral cavity cancer. Further multicenter studies will be required to assess the impact of TTI and adherence to guidelines on the survival of oral cavity cancer patients.

Adjuvant chemoradiotherapy plus PD-1 inhibitor for pN3 gastric cancer: a randomized, multicenter, Phase III trial.

D2 surgery followed by adjuvant chemotherapy has been established as the standard of care for patients with locally advanced gastric cancer in Asian countries. However, its efficacy is still unsatisfactory, especially for pathological N3 disease. The RACING trial is a randomized, multicenter, Phase III trial designed to compare the efficacy and safety of chemotherapy alone versus chemotherapy in combination with PD-1 inhibitor and radiotherapy in patients with pN3 gastric or gastroesophageal junction adenocarcinoma. A total of 433 patients will be assigned at a 1:1 ratio to the two arms. The primary end point is the 3-year disease-free survival rate. The secondary end points include the 3-year overall survival rate, 3-year local recurrence-free survival rate, treatment-related adverse events and quality of life.Clinical Trial Registration: NCT04997837 (ClinicalTrials.gov).

Venetoclax plus low intensity chemotherapy for adults with acute lymphoblastic leukemia

In acute lymphoblastic leukemia (ALL), the BCL2 inhibitor venetoclax may enhance the efficacy of chemotherapy allowing dose reductions that reduce toxicity. We designed a phase 1b study of venetoclax plus attenuated chemotherapy to determine the recommended phase 2 dose (RP2D) of venetoclax. The study enrolled 19 patients with ALL either newly diagnosed (≥60 years, n=11 [B-cell, n=8; T-cell, n=3]) or R/R (≥18 years, n=8 [B-cell, n=3; T-cell, n=5]). Venetoclax was given for 21 days with each cycle of mini-hyper-CVD (cyclophosphamide, vincristine, dexamethasone alternating with methotrexate and cytarabine). There were no dose limiting toxicities at dose level (DL) 1 (n=3, 400 mg/day) or DL2 (n=6, 600 mg/day); DL2 was the RP2D and explored further (n=10). The most common non-hematologic adverse events were grade 3+ infections. There were no deaths within 60 days and no patients discontinued therapy for toxicity. There was no tumor lysis syndrome, hepatotoxicity, or prolonged cytopenias. Among patients with newly diagnosed ALL, 10/11 (90.9%) achieved a measurable residual disease-negative (<0.01% sensitivity) complete remission (CR) including 6 patients with hypodiploid TP53 mutated ALL. All patients in CR bridged to hematopoietic stem cell transplant (n=9) or completed protocol (n=1). With a median follow-up of 60.0 months, median disease-free survival (DFS) for patients with newly diagnosed ALL was 54.6 months (95% CI: 35.5 months – NA) with a 2-year DFS rate of 90% (95% CI, 71% – 100%). Among patients with R/R ALL, 3/8 (37.5%) achieved CR. In summary, for patients with newly diagnosed ALL, venetoclax plus mini-HCVD is well-tolerated with promising efficacy. NCT03319901

Effectiveness of ultrasound-guided vacuum-assisted excision for treating benign breast lesions.

Ultrasound‑guided vacuum-assisted excision (UGVAE) and breast biopsy are widely used for the diagnosis and treatment of both benign and suspicious breast lesions. In this retrospective study, we aimed to determine the safety of UGVAE for benign breast lesions and provide guidance for clinical practice. We analyzed clinical and pathological data of female patients who had undergone UGVAE between January 2015 and December 2017 at our institution. All breast lesions were categorized according to the Breast Imaging Reporting and Data System (BI-RADS) before performing UGVAE. In our study cohort, UGVAE was used to resect 10,378 breast lesions from 5789 patients, and selected clinical and histopathological data were analyzed. The most common adverse events were postoperative bleeding (0.24%) and skin hypersensitivity (0.67%). The residual lesion rate was 2.27%. Fibroadenomas accounted for most of the benign lesions (7932 of 10,193; 77.82%). Breast cancer was diagnosed in 150 lesions from 128 patients. Multivariable binary logistic regression analyses showed that older age (odds ratio [OR] = 2.034, 95% confidence interval [CI]: 1.668-2.480, p < 0.001), higher BI-RADS category (OR = 9.514, 95% CI: 6.790-13.332, p < 0.001), and larger legion size (OR = 1.048, 95% CI: 1.019-1.077, p = 0.001) were associated with an increased likelihood of breast cancer. Ninety-six patients with breast cancer had undergone follow-up treatment, achieving a 3-year disease-free survival rate of 97.2% and a 3-year overall survival rate of 100%. UGVAE is a safe and effective means of removing benign breast lesions, causing minimal postoperative trauma and fewer complications compared with open surgery. Moreover, UGVAE had little impact on the follow-up treatment and survival of patients diagnosed with breast cancer.

Long term outcomes from the early days of minimally invasive thymoma surgery for Myasthenia Gravis patients: a follow-up of 19 years.

Long-term survival outcomes are crucial for accurately determining the effectiveness of treatment in an indolent disease like thymoma. We aimed to analyze the clinical findings in terms of survival and relapse patterns with a median follow up of 105 months (8.7 years) in patients with thymoma and myasthenia gravis who underwent minimally invasive surgery between 2002 and 2015. A total of 59 pathologically confirmed Masaoka Stage I and II thymoma patients with Myasthenia Gravis (MG) who underwent minimally invasive thymoma resection were included in this study. Primary aim of this study is to evaluate recurrences, overall and disease free survival in patients with a thymoma and MG in the long run. We also aimed to study the changes in Myasthenia Gravis medication during the follow-up. The mean age of the patients was 47.6 +/13.5 years. Seventeen patients were at Masaoka Stage I and 42 were at Masaoka Stage II. The median follow-up time was 105 months. The mean size of the tumor was 3.6 cm +/16.2 cm. Twenty-one patients (35%) received adjuvant radiotherapy. There was no postoperative mortality and median length of hospital stay was 4 days. Two patients developed recurrences both presented with pleural metastases. Eight patients died because of non-oncologic pathologies. 10-year disease free survival and overall survival rates were calculated to 96.6% and 86.4% respectively. The 10-year survival analysis and current myasthenic status of stage I-II thymoma patients with myasthenia gravis who underwent minimally invasive surgery demonstrate that these procedures are both safe and effective.

Effect of postoperative complications on 5-year survival following laparoscopic surgery for resectable colorectal cancer: a retrospective study

PurposeThe purpose of this study was to investigate the effects of postoperative complications on long-term survival after laparoscopic surgery for resectable colorectal cancer.MethodsWe retrospectively included 204 patients who underwent laparoscopic surgery for colorectal cancer from January 2016 to June 2020.ResultsOverall, 68 (33.3%) patients had postoperative complications, twelve (17.6%) of which were classified as Clavien–Dindo class 3a or higher. The 5-year overall survival rate of the non-complication and complication groups were 93.0% and 81.7%, respectively (p = 0.048; Kaplan–Meier analysis and log-rank test), and those among patients with stage III disease were 87.0% and 61.3%, respectively (p = 0.045). The 5-year disease-free survival rates were 85.6% and 77.4%, respectively (p = 0.042). Multivariable Cox proportional-hazards analysis revealed that nodal stage (hazard ratio, 8.392; 95% confidence interval, 1.892–37.175; p = 0.005) was an independent prognostic factor for overall survival, and postoperative complications (hazard ratio, 2.996; 95% confidence interval, 1.076–8.340; p = 0.036) were independent prognostic factors for disease-free survival.ConclusionPostoperative complications were associated with poor oncological outcomes, especially among patients with stage III colorectal cancer, and independent prognostic factors for disease-free survival.

The Ongoing Development of Watch and Wait

AbstractThe nonoperative management of rectal cancer, known as watch and wait (W&amp;W), has gained increasing acceptance in recent years. This approach is based on using complete clinical response (cCR) as a marker for complete pathological response (pCR) following neoadjuvant chemoradiation (nCRT). Advances in nCRT regimens have resulted in higher tumor regression rates, making W&amp;W a viable option for selected patients. This study presents the historical evolution and efficacy of the W&amp;W strategy and offers modern recommendations based on recent clinical findings. Key findings include an 85 to 92% 5-year disease-free survival rate in patients achieving cCR, highlighting the potential for improved quality of life and reduced morbidity without compromising survival outcomes.

Phase II trial evaluating the long-term efficacy and peripheral sensory neuropathy of capecitabine plus oxaliplatin (XELOX) as adjuvant therapy in Japanese patients with operated stage III colon cancer

Adjuvant oxaliplatin plus capecitabine (XELOX) therapy is recommended for patients with curatively resected colon cancer. However, prospective data on its practical application in Japanese patients are limited. Therefore, we aimed to conduct a long-term clinical evaluation of the efficacy and safety of adjuvant XELOX in patients with curatively resected stage III colon cancer (MCSCO-1024). This prospective, multi-center, open-label, single-arm, phase II study enrolled patients with curatively resected stage III colon cancer. The treatment protocol consisted of a 120-minute intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and two divided doses oral capecitabine (2000 mg/m2/day) for 14 days in a 3-week cycle, totaling eight cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints were 5-year overall survival and long-term prognosis of peripheral sensory neuropathy. A total of 196 patients were enrolled between November 2011 and August 2014 (34 months). The 3-year DFS rate was 73%, and the 5-year overall survival rate was 87%. The overall incidence of peripheral sensory neuropathy was 17%, with a 1% rate of grade 3 neuropathy after 5 years. Adjuvant XELOX demonstrated utility and safety in the clinical management of Japanese patients with stage III colon cancer.

Correlation Between the Extent of N1 Lymph Node Station Examination and Prognosis in Stage I Nonsmall Cell Lung Cancer Patients: One Station is Insufficient

BackgroundExamination standards for hilar and intrapulmonary (N1) lymph nodes (LNs) have been debated. The objective of this study was to assess the prognostic significance of the extent of examination for N1 LN stations in patients with pathological stage I nonsmall cell lung cancer (NSCLC). MethodsA total of 1868 patients were identified and divided into 3 groups on the basis of the number of N1 stations examined: group A (≥3 stations), group B (2 stations) and group C (1 station). Moreover, we investigated the prognostic significance of each individual N1 station examined. The primary outcome was 5-year disease-free survival (DFS). ResultsOverall, 1062, 607, and 199 patients were in groups A, B, and C, respectively. The baseline demographic and clinical characteristics were similar among the groups, except for the tumor side. The 5-year DFS rates were comparable between groups A and B (85.1% vs. 82.7%, P = .3), both of which were significantly greater than that of group C (74.4%) (P < .01). Similar results were observed for the corresponding 5-year overall survival rates. The number of N1 stations examined was an independent predictor in multiple analyses. Additionally, the examination of stations 10 and 13 were independent favorable predictors for 5-year DFS. ConclusionFor patients with pathological stage I NSCLC, examination of only 1 N1 station is insufficient. Examinations of a minimum of two N1 stations, including stations 10 and 13, is recommended to obtain the optimal survival benefit.

Clinicopathological Characteristics and Perioperative Treatment of Epstein-Barr Virus-Associated Gastric Cancer: A Retrospective Study.

The clinicopathological characteristics and perioperative treatment outcomes of patients with EBVaGC who underwent radical gastrectomy in Tianjin Medical University Cancer Hospital from September 2016 to May 2022 were retrospectively reviewed. Disease-free survival (DFS) was analyzed and Cox regression analysis was performed to identify risk factors. The study cohort included 128 patients with EBVaGC. Histologically, 126 (98.4%) patients had adenocarcinoma and only 2 (1.6%) had adenosquamous carcinoma. In addition, 18 (14.1%) had nerve invasion and 29 (22.7%) had vascular invasion. Notably, 41 (32.0%) patients had tumors in the proximal stomach and 69 (53.9%) had no lymph node metastasis. Proficient mismatch repair was confirmed in all 104 patients with available results. Overall, 16 (12.5%) patients received neoadjuvant therapy, 81 (63.3%) received adjuvant therapy, and 10 (7.8%) received perioperative immunotherapy combined with chemotherapy. In total, 22 patients experienced disease progression or had died. The 3-year DFS rate was 75.0%. DFS was relatively poorer for patients with advanced tumor (T) stage, lymph node (N) stage, disease stage, and vascular invasion. EBVaGC had unique clinicopathological characteristics and prognosis. Advanced T, N, and disease stages, in addition to vascular invasion, were predictive of poorer DFS. However, the efficacy of perioperative treatment of EBVaGC remains uncertain.

Monitoring of Circulating Tumor DNA and Indication of De-Escalation Adjuvant Targeted Therapy for EGFR-Mutated NSCLC After Complete Resection

IntroductionEGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA EGFR-mutated NSCLC. Nevertheless, adapting this approach to include a molecular residual disease (MRD)-guided de-escalation strategy warrants further investigation. MethodsFrom January 2019 to December 2022, 71 patients with stages I to III NSCLC and EGFR (exon 19 deletion or L858R) mutations were enrolled in this observational study. A total of 375 blood samples were analyzed using the MRD_Navigator assay. Among them, 27 patients suspended EGFR TKI treatment based on undetectable MRD and were thus included in the adaptive, de-escalation group. ResultsOverall, the sensitivity of longitudinal MRD was 86.2%. Only four patients (11.8%) recurred with longitudinal undetectable MRD, indicating a negative predictive value of 88.2%. Of the patients who had detectable MRD after surgery, nine subsequently received EGFR TKI treatment, with only one (11.1%) achieving persistent circulating tumor DNA clearance post–EGFR TKI. Furthermore, 22 patients with stages IB to III disease who had previously suspended their TKI treatment based on undetectable MRD were included in the adaptive group, with an average duration of TKI 3.9 (range: 0–35.0) months. The 2-year disease-free survival rate of these 22 patients was 80.2%, and the median was not reached. Five patients (n = 5 of 22, 22.7%) had disease recurrence during the period of drug cessation but were stable under EGFR TKI treatment until the latest follow-up. Two patients remained in complete remission. ConclusionsOur initial findings underscore the potential of an adaptive, de-escalation approach to adjuvant EGFR TKIs based on circulating tumor DNA-MRD monitoring.