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Background Tumor regression grade (TRG) after neoadjuvant therapy is reportedly predictive of prognosis in esophageal cancer patients, as lack of a response to neoadjuvant therapy is associated with a poor prognosis. However, there is little information available on the timing and pattern of recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma (TESCC) that takes into consideration TRG after neoadjuvant chemoradiotherapy (NACRT). Here, in an effort to gain insight into a treatment strategy that improves the prognosis of NACRT non-responders, we evaluated the patterns and timing of recurrence in TESCC patients, taking into consideration TRG after NACRT. Methods A total of 127 TESCC patients treated with NACRT and esophagectomy between 2009 and 2017 were enrolled in this observational cohort study. TRGs were assigned based on the proportion of residual tumor cells in the area (TRG1, ≥1/3 viable cancer cells; 2, < 1/3 viable cancer cells; 3, no viable cancer cells). We retrospectively investigated the timing and patterns of recurrence and the prognoses in TESCC patients, taking into consideration TRG after NACRT. Results The 127 participating TESCC patients were categorized as TRG1 (42 patients, 33%), TRG2 (56 patients, 44%) or TRG3 (29 patients, 23%). The locoregional recurrence rate was higher in TRG1 (36.4%) patients than combined TRG2–3 (7.4%) patients. Patients with TRG3 had better prognoses, though a few TRG3 patients experienced distant recurrence. There were no significant differences in median time to first recurrence or OS among patients with locoregional or distant recurrence. There was a trend toward better OS in TRG2–3 patients with recurrence than TRG1 patients with recurrence, but the difference was not significant. Conclusions NACRT non-responders (TRG1 patients) experienced higher locoregional recurrence rates and earlier recurrence with distant or locoregional metastasis. TRG appears to be useful for establishing a strategy for perioperative treatments to improve TESCC patient survival, especially among TRG1 patients. (303 words).

Purpose The differences in tumor behavior between adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the esophagogastric junction (EGJ) have yet to be well investigated. The purpose of this study was to gain insights that can contribute to tailored treatments and follow-up strategies by analyzing the correlation between histological subtypes and oncological outcomes. Methods A retrospective analysis was used to determine the characteristics of the histological subtypes of EGJ cancer by comparing the appearance of postoperative recurrence. A total of 102 consecutive patients with pathological stage IIA to IVA EGJ cancer, who underwent R0 surgery in our department from 2004 to 2020, were enrolled. The recurrence pattern, timing, survival, and potential prognostic factors were compared. Results After a median follow-up time of 70.1 months, the AC group demonstrated comparable lymph node failure-free survival (P = 0.291) and significantly worse non-lymphogenous recurrence-free survival (P = 0.035) than did the SCC group. A significantly longer period from surgery to recurrence was also observed in the AC group (P = 0.029). Multivariate analysis indicated that histological subtype (P = 0.015, 95% CI 1.24–7.28) was significantly correlated with the incidence of non-lymphogenous recurrence. Conclusions The pattern and timing of postoperative recurrence were significantly different between the histological subtypes of EGJ cancer. Compared with EGJ SCC, EGJ AC may have a greater tendency toward non-lymphogenous progression and a greater propensity for longer surgery-to-recurrence periods.

Curative gastrectomy and adjuvant chemotherapy using S-1 is a standard treatment for stage II/III gastric cancer in Japan. The purpose of the present study was to evaluate the prognostic relevance of fibroblast growth factor receptor (FGFR)2 expression in patients with stage II/III gastric cancer that underwent postoperative adjuvant chemotherapy with S-1. Formalin-fixed paraffin-embedded surgical specimens were retrospectively examined in 167 patients with stage II/III gastric cancer that underwent curative gastrectomy followed by adjuvant S1 chemotherapy. FGFR2 expression was measured using immunohistochemistry (IHC) staining. The IHC results for FGFR2 were as follows: Grade 1+, 32; grade 2+, 80; grade 3+, 55 patients. The FGFR2 expression level was not significantly associated with relapse-free or overall survival rates. However, in the diffuse type, the FGFR2 expression level tended to be negatively correlated with relapse-free survival. In particular, the proportion of patients who recurred >5 years following surgery was significantly larger in the FGFR2 grade 3+ group than in the grade 1+, 2+ group (4/22 vs. 1/35; P=0.047). The recurrent sites of long-term failure were mostly peritoneum among the diffuse type. To the best of our knowledge, the present study indicated for the first time that FGFR2 could predict long-term failure of adjuvant S-1 chemotherapy in curative advanced gastric cancer. There was no interaction between FGFR2 expression and patient survival outcomes in stage II/III gastric cancer. Patients with FGFR2 3+ in stage II/III gastric cancer should carefully be followed-up for >5 years after surgery.

Background In cancer survival analyses using population-based data, researchers face the challenge of ascertaining the timing of recurrence. We previously developed algorithms to identify recurrence of breast cancer. This is a follow-up study to detect the timing of recurrence. Methods Health events that signified recurrence and timing were obtained from routinely collected administrative data. The timing of recurrence was estimated by finding the timing of key indicator events using three different algorithms, respectively. For validation, we compared algorithm-estimated timing of recurrence with that obtained from chart-reviewed data. We further compared the results of cox regressions models (modeling recurrence-free survival) based on the algorithms versus chart review. Results In total, 598 breast cancer patients were included. 121 (20.2%) had recurrence after a median follow-up of 4 years. Based on the high accuracy algorithm for identifying the presence of recurrence (with 94.2% sensitivity and 79.2% positive predictive value), the majority (64.5%) of the algorithm-estimated recurrence dates fell within 3 months of the corresponding chart review determined recurrence dates. The algorithm estimated and chart-reviewed data generated Kaplan–Meier (K-M) curves and Cox regression results for recurrence-free survival (hazard ratios and P -values) were very similar. Conclusion The proposed algorithms for identifying the timing of breast cancer recurrence achieved similar results to the chart review data and were potentially useful in survival analysis.

Colorectal cancer with peritoneal metastases (CRCPM) exhibits high recurrence post-cytoreductive surgery (CRS). This study evaluated tumor tissue biomarkers and combined circulating tumor DNA (ctDNA) and methylation analysis via ultra-deep next-generation sequencing (NGS) for recurrence prediction. CRCPM patients undergoing surgery were enrolled (n=21). Blood samples was collected at preoperative and postoperative, and tumor and adjacent tissues were collected. NGS assessed ctDNA and methylation in blood samples, while tumor mutations and methylation were analyzed in tumor. Recurrence was determined via imaging. Outcomes included progression-free survival (PFS) and overall survival (OS). Of 17 patients with paired pre-/postoperative ctDNA testing, preoperative ctDNA levels were higher in those with extraperitoneal metastases versus peritoneal-only disease (0.1064 vs 0.0037). Postoperative ctDNA positivity correlated with 100% peritoneal recurrence. ctDNA-positive subgroups showed shorter PFS (HR=2.5; 95% CI:1.6-6.6). Patients persistently ctDNA-negative pre-/postoperatively had improved PFS versus those with positivity (HR=5.07; 95% CI:0.53-48.38). ctDNA methylation positivity was observed in all extraperitoneal metastasis cases and 70% of peritoneal-only cases. Baseline methylation positivity predicted worse OS overall and in peritoneal-only subgroups. Postoperative dual negativity for ctDNA and methylation correlated with better OS. Tumor mutations in EPHB1 ( = 0.012), ARFRP1 ( = 0.048), and ATR ( = 0.048) were significantly associated with PFS. Dynamic ctDNA and methylation monitoring, and tumor mutation profiling, may serve as sensitive biomarkers for early recurrence detection in CRCPM underwent CRS. These tools could enhance recurrence prediction and guide clinical management.

Background Adjuvant chemotherapy improves survival in patients with gastric cancer. However, the relationship between the timing of adjuvant chemotherapy and survival has not been investigated. Methods Patients with D2-resected stage 2 and 3 gastric cancer that received adjuvant chemotherapy from 2005 to 2011 at Yonsei University Health System were included. The patients were grouped according to intervals between surgery and adjuvant chemotherapy. Results Among 840 patients, the interval from surgery to the start of adjuvant therapy was less than 4 weeks in 337 (40.1 %) patients (early group), 4–8 weeks in 467 (55.6 %) patients (intermediate group), and more than 8 weeks in 36 (4.3 %) patients (late group). The 5-year RFS was 55.7 % in the early group, 54.4 % in the intermediate group, and 43.6 % in the late group ( p  = 0.076). The corresponding 5-year OS rates were 63.4, 62.8, and 51.7 % ( p  = 0.037). Conclusions There is insufficient evidence to suggest starting adjuvant chemotherapy within 4 weeks after surgery for patients with D2 resected stage 2 and 3 gastric cancer. However, delayed treatment of adjuvant chemotherapy after 8 weeks showed worse survival outcomes than early and intermediate treatment initiation, suggesting that adjuvant chemotherapy should be considered start within 8 weeks after radical resection.

Background There is no consensus regarding the optimal time to initiate adjuvant chemotherapy after surgery for stage III colon cancer, and the relevant postoperative complications that cause delays in adjuvant chemotherapy are unknown. Methods Eligible patients aged ≥66 years who were diagnosed with stage III colon cancer from 1992 to 2008 were identified using the linked Surveillance, Epidemiology, and End Results-Medicare database. Kaplan-Meier analysis and a Cox proportional hazards model were utilized to evaluate the impact of the timing of adjuvant chemotherapy on overall survival (OS). Results A total of 18,491 patients were included. Delayed adjuvant chemotherapy was associated with worse OS (9–12 weeks: hazard ratio [HR] = 1.222, 95% confidence interval [CI] = 1.063–1.405; 13–16 weeks: HR = 1.252, 95% CI = 1.041–1.505; ≥ 17 weeks: HR = 1.969, 95% CI = 1.663–2.331). The efficacies of adjuvant chemotherapy within 5–8 weeks and ≤4 weeks were similar (HR = 1.045, 95% CI = 0.921–1.185). Compared with the non-chemotherapy group, chemotherapy initiated at ≥21 weeks did not significantly improve OS (HR = 0.882, 95% CI = 0.763–1.018). Patients with postoperative complications, particularly cardiac arrest, ostomy infection, shock, and septicemia, had a significantly higher risk of a 4- to 11-week delay in adjuvant chemotherapy ( p  < 0.05). Conclusions Adjuvant chemotherapy initiated within 8 weeks was acceptable for patients with stage III colon cancer. Delayed adjuvant chemotherapy after 8 weeks was significantly associated with worse OS. However, adjuvant chemotherapy might still be useful even with a delay of approximately 5 months. Moreover, postoperative complications were significantly associated with delayed adjuvant chemotherapy.

BackgroundAdjuvant S-1 monotherapy prolongs the survival of patients with pathological stage II or III gastric cancer undergoing D2 gastrectomy. This therapeutic regimen is standard in Japan. Unfortunately, some patients who undergo this treatment suffer from recurrent disease. However, information regarding the timing and site-specific trends of recurrence is insufficient.MethodsAmong 396 patients who underwent D2 gastrectomy followed by adjuvant S-1 monotherapy between 2008 and 2012, 122 experienced a recurrence. We retrospectively determined the timing and sites of recurrence.ResultsThe median RFS of the 122 patients was 19.5 months, and their 1-, 3- and 5-year RFS rates were 67.2%, 23.0% and 5.7%, respectively. There were no significant differences in RFS among disease substages. Local recurrence, lymph node involvement and peritoneal and hematogenous metastases were found in 6, 25, 63 and 42 patients, respectively. Approximately 10% of patients presented with contemporaneous sites of recurrence. Local recurrence and lymph node metastasis plateaued 3 years after gastrectomy. Peritoneal and hematogenous metastasis increased within 5 years after surgery. In patients with hematogenous metastasis, the number of liver metastases plateaued but increased in others.ConclusionsIn patients with recurrent disease who underwent D2 gastrectomy followed by adjuvant S-1 monotherapy, 80% of recurrences occur within 3 years after gastrectomy. The timing of recurrence is not significantly different among substages. Although the rates of local recurrence and lymph node and liver metastasis plateau after 3 years, peritoneal and the other hematogenous metastases increase within 5 years.

Background The purpose of this research was to examine the probability of ipsilateral breast cancer recurrence in individuals whose RT was delayed after the first chemotherapy and surgery. Purpose To analyze the effect of delaying RT for breast cancer patients (by more than 6 weeks after treatment). Methodology A retrospective analysis comprised 136 female breast cancer patients treated at the Baghdad Centre for Radiation Oncology and Nuclear Medicine from 2021 to May 2022. External beam radiation was started more than 6 weeks after chemotherapy was finished for all patients who also had surgery. Clinical examination and ultrasound were part of the follow-up process. Results Patients’ ages varied from 28 to 71, and the majority (83%) had a mastectomy. The majority of cases (95.5%) were diagnosed as invasive ductal carcinoma on histopathology, with 49.6% being at stage 2 and 42.6% being at stage 3. Seventy-six percent of patients tested positive for hormones. Although 10 patients (7.35%) acquired distant metastases within 5 years, only 2 (1.47%) had local recurrence because of the delay in RT. Specifically, 91.1% had complete local control with no evidence of disease spread. Conclusion Delaying RT by more than 6 weeks in patients with breast cancer did not substantially affect local control, according to the results of a new research, the first of its type in Iraq.