Distant Recurrence Research Articles

The prognostic and predictive value of the luminal-like subtype in hormone receptor-positive breast cancer: an analysis of the DATA trial.

This study determines the prognostic value of the luminal-like subtype in patients with hormone receptor-positive breast cancer and explores whether the efficacy of extended anastrozole therapy differs between patients with luminal A-like versus luminal B-like tumours. The phase III DATA study (NCT00301457) examined the efficacy of 6 versus 3 years of anastrozole in postmenopausal women with early-stage hormone receptor-positive breast cancer who had received 2-3 years of tamoxifen. Patients with available formalin-fixed paraffin-embedded tissue blocks were identified and classified by immunohistochemical luminal-like subtype. Distant recurrence (DR) and breast cancer-specific mortality (BCSM) were compared by luminal-like subtype and treatment arm using competing risk methods. This study included 788 patients: 491 had a luminal A-like tumour and 297 had a luminal B-like tumour. The median follow-up time was 13.1 years. Patients with luminal B-like tumours experienced a higher risk of DR [subdistribution hazard ratio (sHR) 1.44, 95% confidence interval (CI) 1.03-2.01, P= 0.03] and BCSM (sHR 1.68, 95% CI 1.15-2.45, P= 0.008) than patients with luminal A-like tumours. The efficacy of extended anastrozole therapy differed between patients with luminal A-like tumours (DR: sHR 0.51, 95% CI 0.30-0.88, P= 0.02; BCSM: sHR 0.39, 95% CI 0.19-0.82, P= 0.01) and patients with luminal B-like tumours (DR: sHR 2.09, 95% CI 0.96-4.53, P= 0.06; BCSM: sHR 2.36, 95% CI 0.80-7.00, P= 0.12) (P-interaction= 0.03 and P-interaction= 0.06, respectively). In patients with hormone receptor-positive breast cancer, the luminal B-like subtype was associated with a significantly worse prognosis when compared with the luminal A-like subtype. Extended anastrozole therapy halved the risk of DR and BCSM in patients with luminal A-like tumours, whereas no effect was seen in patients with luminal B-like tumours.

Malignant phyllodes tumors with sarcomatous components: A histopathologic and molecular study.

Malignant phyllodes tumors (MPTs) with sarcomatous components are often associated with substantial risks for local and distant recurrences. A more comprehensive characterization of their clinicopathological features and molecular profiles may offer significant potential innovative therapeutic strategies. A total of ten cases were collected with eight cases undergoing DNA next-generation sequencing (NGS). The clinicopathological characteristics, prognostic information, and genomic profiles were compared to those of MPTs without sarcomatous components. Compared to MPT without sarcomatous components, no significant differences were found in age, tumor position, tumor size, menopausal status, or presence of fibroadenoma (p > 0.05). MPTs with osteosarcoma components had a poor prognosis either compared with other sarcomatous components (p = 0.027) or MPTs without sarcomatous components (p = 0.033). A notably high frequency of mutations was observed in several key genes within MPTs exhibiting sarcomatous components: TP53 (n = 6, 75.0 %), MUC16 (n = 4, 50.0 %), PTCH1 (n = 3, 37.5 %), and APC (n = 3, 37.5 %). In MPTs characterized by sarcomatous components, MCL1 (n = 6, 75.0 %) and MYC (n = 5, 62.5 %) demonstrated a notably high frequency of amplification. The NOTCH signaling pathway was significantly associated with MPTs characterized by sarcomatous components (13.6 % vs 75.0 %, p = 0.001). The presence of an osteosarcoma component may serve as an indicator for unfavorable prognosis. Activating mutations in TP53 have been identified in these tumors. Furthermore, it typically facilitates tumor formation and progression via the NOTCH signaling pathway. These findings may offer valuable insights for clinical prognosis and identify potential therapeutic targets.

The pathologic and genomic evolution of primary malignant phyllodes tumors of the breast: retrospective cohort study and case-control genomic analysis.

In patients with phyllodes tumors of the breast, the presence of mediator of RNA polymerase II transcription subunit 12 homolog mutations (MED12m) and a history of previous fibroadenoma may predict better outcomes. To aid in the prognostication of malignant phyllodes tumors of the breast (B-MPT), we assessed the prognostic value of fibroadenoma-like areas (supposed to have stemmed from a pre-existing fibroadenoma) and MED12m, in patients with resected primary B-MPTs. We conducted a single-center, retrospective, cohort study including all consecutive patients aged ≥18 years old, with non-metastatic B-MPT, who underwent surgery from January 2000 to December 2021. The endpoints were the cumulative incidences of all recurrences, according to the presence of fibroadenoma-like areas, reviewed by 3 reference pathologists. A nested, case-control genomic analysis was performed to evaluate the association between MED12m, the presence of fibroadenoma-like areas, and cancer recurrences. Eight-nine patients were included, with 47% of tumors exhibiting Fibroadenoma-Like Areas (FLA+). These areas were not significantly associated with local recurrence (5-year cumulative incidence in FLA+ vs FLA-: 13.0, 95%CI [4.6-25.9] vs 23.6, 95%CI [11.9-37.5]; P = .14) or distant recurrence (5-year cumulative incidence in FLA+ vs FLA-: 12.5, 95%CI [4.5-25.0] vs 8.9, 95%CI [2.8-19.5], P = .61), at a median follow-up of 6.7 years. MED12m was not associated with distant recurrences or the presence of fibroadenoma-like areas. Half of B-MPTs are characterized by the presence of fibroadenoma-like areas. This pathologic feature is not significantly associated with lower distant and local recurrences nor with the presence of MED12 mutations.

Gene expression profiling tests to guide adjuvant chemotherapy decisions in lymph node-positive early breast cancer: a systematic review.

To systematically review the effectiveness of gene expression profiling tests to inform adjuvant chemotherapy decisions in people with hormone receptor-positive (HR+), lymph node-positive (LN+) breast cancer. This systematic review assessed the effectiveness of Oncotype DX, Prosigna, EndoPredict and MammaPrint for guiding adjuvant chemotherapy decisions in HR+ early breast cancer with 1-3 positive nodes, in terms of prognostic ability, prediction of chemotherapy benefit, impact on chemotherapy decisions, quality of life and anxiety. Searches covered MEDLINE, EMBASE and Cochrane databases in April 2023. Fifty-five articles were included. All four tests were prognostic for distant recurrence in LN+ patients. The RxPONDER trial reported no chemotherapy benefit in post-menopausal LN+ patients with low Oncotype DX (RS 0-25), whilst pre-menopausal patients had statistically significant chemotherapy benefit. An RCT reanalysis of Oncotype DX (SWOG-8814) suggested greater chemotherapy benefit with higher RS in post-menopausal LN+ patients. The MINDACT trial reported that LN+ patients with high clinical risk and low MammaPrint risk had a non-statistically significant chemotherapy benefit, but was not designed assess differential chemotherapy benefit per risk group. Decisions to undergo chemotherapy reduced by 12-75% following Oncotype DX testing in LN+ patients in the UK and Europe. No studies in LN+ populations were identified for prediction of chemotherapy benefit by Prosigna or EndoPredict; or for chemotherapy decisions for Prosigna, EndoPredict or MammaPrint; or for anxiety or quality of life impact for any test. All four tests have prognostic ability in LN+ patients. Evidence on predictive benefit is weaker, with equivocal evidence that Oncotype DX may predict chemotherapy benefit in LN+ post-menopausal patients. Use of Oncotype DX leads to fewer patients being recommended chemotherapy.

Tumor tissue modified viral (TTMV)-HPV DNA as a biomarker of treatment efficacy for definitive chemoradiation in anal squamous cell carcinoma: A step towards truly personalized therapy.

10 Background: Cell-free circulating tumor tissue modified viral DNA (ctDNA) has been used as a biomarker to detect recurrence for anal squamous cell carcinoma (ASCC). However, its value in informing treatment modification during definitive chemoradiation (CRT) has yet to be explored. We evaluated ctDNA response during and at completion of definitive CRT to establish patterns of disease response and inform future studies to personalize treatment. Methods: From 11/2022 to 6/2024, 13 consecutive patients with biopsy proven, non-metastatic ASCC received definitive CRT and had ctDNA testing using a commercially available droplet digital quantitative PCR assay. ctDNA testing was done at baseline (pre-CRT), week 4 of CRT, and/or end of CRT, 1-3 months post-CRT, and every 6 months thereafter. CRT included concurrent 5FU/MMC (or capecitabine/MMC) and radiotherapy according to RTOG 0529. Treatment response assessment included: physical exam, anoscopy, and imaging with PET/CT, CT C/A/P +/- MRI abdomen and pelvis. Results: 13 patients had ctDNA testing and 11 patients had HPV-positive ASCC and tested positive for ctDNA. The 11 patients with detectable baseline ctDNA were included in this analysis. The median age at diagnosis was 63 years old. Staging included: 1- Stage IIA, 7- Stage IIB, 1- Stage IIIA, 2- Stage IIIC. 1 patient was cN0, while 11 were cN1. With a median follow-up from completion of CRT of 13 months, 4 patients have persistent or recurrent disease: 2 with distant metastases, 1 with persistent local disease (1 month post-CRT), and 1 with local and distant recurrence. Baseline value of ctDNA did not correlate to stage at diagnosis, rate of clearance during CRT, or likelihood of recurrence. 5 of 11 patients cleared ctDNA by week 4 of CRT. Of 5 patients who cleared ctDNA by week 4 of CRT, 4 remain NED and 1 developed distant metastases. Of 6 patients with persistent ctDNA at week 4 of CRT, 3 have persistent or recurrent disease- 1 local persistence 1 month post-CRT, 1 local and distant recurrence 6 months post-CRT, and 1 with distant recurrence 12 months post- CRT. Among 6 patients who cleared ctDNA by the final week of CRT, 1 patient developed recurrent disease. Among the 4 patients in the series with residual/recurrent disease, 3 of them had not cleared ctDNA by the end of CRT. Of 10 patients with ctDNA testing at 1 month post-CRT, 8 had no detectable ctDNA. 2 patients with persistent (1) or recurrent (1) ctDNA at 1 month post-CRT developed disease recurrence- 1 with distant recurrence and 1 with local and distant recurrence. Conclusions: ctDNA assessment during CRT may provide insight into disease response that can predict patterns of failure and facilitate personalized therapy- treatment intensification, deintensification, or additional testing to detect early metastatic disease. Larger studies and clinical validation are needed.

Evaluation of event-free survival (EFS) as a surrogate for overall survival (OS) in patients with locally advanced esophageal carcinoma (LA EC) receiving definitive chemoradiotherapy (dCRT).

412 Background: Drug development in esophageal cancer is rapidly evolving, and identifying surrogates for patient outcomes to accelerate clinical drug development remains an important unmet medical need. Although early clinical endpoints such as EFS, disease free survival (DFS) are proven to be valid surrogates for overall survival (OS) in early esophageal (Ajani JA et al. 2022), gastric (Oba K et al. 2013; Wainberg ZA et al. 2023), and gastroesophageal junction tumors (Ronellenfitsch U. et al. 2013) after disease resection, there are no such surrogacy data evaluating patients who underwent non-operative management. Specifically, there has been no prior systemic evaluation of the predictive value of EFS as a surrogate for OS among LA EC patients treated with dCRT. This study evaluated the trial-level correlation between EFS and OS in unresectable LA EC patients receiving dCRT. Methods: A systematic literature review was conducted to identify randomized controlled trials (RCTs) of dCRT interventions in unresectable LA EC (search cutoff date: April 2023). Studies reporting EFS (or similar outcomes such as progression free survival (PFS), defined as time from randomization to local, regional, or distant recurrence, or death) and OS were included. EFS and OS hazard ratios (HRs) of each treatment comparison were extracted. Correlation between the log(HR) of EFS and OS was assessed using weighted linear regression (WLR). The coefficient of determination (R 2 ) was used to evaluate the strength of the correlation. A good surrogate was defined as an R 2 ≥ 0.65 (Ciani et al . 2017) or an R 2 ≥ 0.75 (Lassere et al . 2008). Leave-one-out cross-validations and sensitivity analyses were conducted to assess the robustness of the WLR model and correlation analyses, respectively. Results: The final analysis included 14 between-treatment comparisons from 11 RCTs (total number of patients = 2,812). We found a strong statistical correlation between EFS and OS, with an estimated slope coefficient of 0.91 ( p < 0.001) and R 2 of 0.80 (95% confidence interval [CI]: 0.38, 0.96). In the leave-one-out cross validation, 71.4% of observed OS HRs fell within the predicted 95% CIs. Sensitivity analyses showed R 2 of 0.75 among studies conducted in China and R 2 of 0.73 after including studies that did not report EFS definition. Conclusions: In a pooled analysis of 11 clinical trials corresponding to over 2800 patients, we observed a strong statistical correlation between EFS and OS outcomes. This analysis supports the utility of EFS as a valid surrogate of OS in patients with unresectable LA EC receiving dCRT.

Investigating the real-world outcomes of single- versus multi-agent preoperative chemoradiotherapy for locally advanced rectal cancer: NCDB analysis from 2004-2020.

61 Background: Fluorouracil-based chemoradiotherapy is the standard initial treatment for locally advanced rectal cancer, demonstrating improved pathological response and reduced local recurrences compared to radiation alone. Fluorouracil-based chemo-radiation therapy has no impact on distant recurrences. Oxaliplatin was tested in addition to fluorouracil-based chemo-radiotherapy in clinical trials to improve pathological complete response (pCR), distant recurrence-free survival, and overall survival. The trial results are conflicting. In this study, we aim to compare single-agent (SA) versus multi-agent (MA) chemotherapy using real-world data from the National Cancer Database (NCDB). Methods: The NCDB was used to identify 39,667 patients with rectal cancer who received concurrent chemoradiotherapy between 2004 and 2020. We compared patients who received SA chemotherapy with those who received MA concurrent chemotherapy. The primary outcomes of interest were overall survival and pCR. The groups were compared using univariate analysis and Cox proportional hazard models to adjust for potential confounding factors. Results: Of 39,667 patients with rectal cancer, 24,452 received single-agent (SA) chemotherapy and 14,215 received multi-agent (MA) chemotherapy. Patients in the SA group were of advanced age, had a greater number of comorbidities (as calculated by the Charleson-Dayo score), were treated within community facilities, had a higher income status, were covered by government insurance, were situated on the east coast, and had lower educational attainment compared to those in the MA group (p<0.05). SA group had higher T4 and N1 disease, however MA group had more N2 disease. Upon survival analysis, patient in MA group had higher survival (41.2 vs 38.9 months, p=0.005), however pCR was significantly higher in SA group (10.4% vs 6.4%, p<0.001). Conclusions: MA chemoradiotherapy for rectal cancer improves survival, with the SA regimen showing enhanced complete pathological response. Differences in baseline characteristics may explain the outcomes. While MA chemotherapy offers modest overall survival benefits, potential toxicity needs to be considered and confirmed in future studies. Comparison between single agent vs multi-agent chemo-radiotherapy group. Outcome Single-agent chemotherapy Multiagent chemotherapy Chi Squared p-value No readmission within 30 days of surgical discharge 22,727 (89.3 %) 12,921 (90.9 %) <0.001 30-day mortality after surgery 360 (1.5 %) 59 (0.5 %) <0.001 90-day mortality after surgery 716 (3.0 %) 158 (1.3%) <0.001 Median duration of surgical admission 6.0 5.0 <0.001 Median survival-vital = deceased (months) 38.9 41.2 0.005 Median survival-vital = alive (months) 66.9 52.0 <0.001 Pathological complete response (pCR) 2,644 (10.4%) 904 (6.4%) <0.001

Correlation of tumoral collagen width with overall survival and tumoral collagen straightness with distant recurrence-free survival in patients with pancreatic ductal adenocarcinoma.

779 Background: Quantitative measurements of fibrillar collagen characteristics has been shown to correlate with survival in several types of malignancy. The aim of this study was to determine whether these characteristics correlate with survival in pancreatic ductal adenocarcinoma. Methods: Patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma at an Allegheny Health Network hospital between 1/1/2019 and 12/31/2023, and for whom archived formalin-fixed paraffin-embedded tumor tissue was available, were included in the study. Clinical and pathologic characteristics were collected from the patient's electronic medical record. Survival data included overall survival (OS), local recurrence-free survival (RFS), and distant RFS. One section of tumor per patient was stained with Picrosirius Red and a representative digital image was obtained with a camera attached to a microscope at 100x magnification. Each image was analyzed with CT-FIRE software to determine averages of collagen fiber width, length, straightness, and angle. Descriptive statistics were initially computed. Log-rank tests were also conducted to compare the OS rate and RFS rate between four different groups (width, length, straightness, angle). Each group was divided into high and low groups, using the mean as cutoff. In the end, multivariate Cox regression was conducted by controlling the confounders including sex, perineural invasion, lymphovascular invasion, and presence of lymph node metastasis to examine the hazard ratios of OS, local RFS, and distant RFS for the four collagen fiber metrics. All statistical analyses were performed via SAS 9.4 under alpha level .05. Results: One hundred three patients met the inclusion criteria. Based on the results of log-rank test, OS was significantly different between high and low collagen width groups, p = .0251. The lower width group had higher survival rate than the upper width group. Also, distant recurrence-free survival was significantly different between high and low collagen straightness groups, p = .0053. The lower straightness group had higher distant RFS rate than upper group. The results of multivariate Cox regression were consistent with the Kaplan-Meier curves. Compared to the high collagen width group, the low collagen width group had a 57% lower chance of dying, hazard ratio = 0.43, 95% CI [0.23, 0.78], p = .0056. The low collagen straightness group had a 60% lower chance of distant recurrence than the high collagen straightness group, hazard ratio = 0.40, 95% CI [0.19, 0.85], p =.0163. Conclusions: Quantitative collagen fiber metrics could help identify patients with resected pancreatic adenocarcinoma who are at risk of earlier death and distant recurrence.

Tumour-free ctDNA detection as a decision tool to support organ preservation in node-negative rectal cancer undergoing neoadjuvant chemotherapy, excision, and observation in the phase II NEO trial (CCTG CO.28).

20 Background: In the NEO trial (CCTG CO.28, NCT03259035) patients with node negative (N0) T1-T3 rectal cancer were treated with neoadjuvant CAPOX/FOLFOX and transanal excision surgery (TES) with the goal of organ preservation. Patients without documented response following neoadjuvant chemotherapy were recommended total mesorectal excision (TME). We present a post-hoc assessment of ctDNA detection in this early-stage population and correlate kinetics with response and outcomes. Methods: Fifty-eight patients enrolled in CO.28. Whole blood was collected in EDTA tubes and processed for future ctDNA analysis at up to six timepoints: pre-chemotherapy, after neoadjuvant chemotherapy (and pre-TES), yearly during surveillance for 3 years and upon progression. A total of 195 samples were analyzed with the Guardant Reveal™ assay: a tissue-free epigenomic assay leveraging >20,000 epigenomic regions for ctDNA detection. Results: Of 48 available pre-treatment samples, ctDNA was detected in 22 (46%). Sensitivity by T-stage was 14% (1/7) for T1, 53% (17/32) for T2, 44% (4/9) for T3 cancers. ctDNA detection was lower following neoadjuvant chemotherapy (4/46, 9%, p<0.001 vs pre-chemotherapy). Of 41 patients with paired pre- and post-chemo samples, 49% (20/41) had undetectable ctDNA at both timepoints, 44% (18/41) had reduced tumour fraction following chemotherapy, the majority of which completely cleared ctDNA (94%; 17/18) and 7% (3/41) had an increased tumour fraction following chemotherapy (67%, 2/3 changing from negative to positive), all three of whom failed to respond to neoadjuvant chemotherapy and had TME recommended (100%). In contrast, of those that cleared ctDNA following chemotherapy, 35% had TME recommended (6/17, p=0.074). Of five recurrences (3 distant, 2 local), all had negative or reduced ctDNA tumour fraction during neoadjuvant therapy before surgical intervention. Among patients with local relapse who were managed with TES, 1/2 (50%) had detectable ctDNA at the time of local progression. No samples were available for those with distant recurrences (3/5) at time of relapse. Conclusions: The Guardant Reveal tissue-free assay was able to detect ctDNA even in this extremely early-stage cohort and identified cancers with inadequate response to therapy and in whom TME was recommended. A tissue-free approach may support timeliness of ctDNA results that would support ctDNA as an additional decision tool with endoscopic and MRI assessments to increase physician and patient comfort with organ preservation. Clinical trial information: 03259035.

Effect of adjuvant radiotherapy after endoscopic resection of early esophagus cancer to prevent new intraluminal mucosal recurrence.

381 Background: Endoscopic resection (ER) is effective for treating T1a early esophageal squamous cell carcinoma (ESCC). Occasional distant metastasis and recurrence are inevitable invasion in depth of muscularis mucosa(MM). Additional surgical resection is an effective means for cure and prevent recurrence, but it imposes a heavy physical burden. Chemoradiation therapy (CRT) is a comparable alternative to surgery. Not all patients will want those additional treatment. Another problem is the occurrence of new esophagus intraluminal mucosal recurrence. After endoscopic treatment, there is an increased risk of scarring and deformity. But there are few reports of the effectiveness of additional RT in suppressing new lesions. This study was designed to verify the efficacy of not only curability but also suppressive effect the occurrence of new lesions additional treatment of T1a(MM) ESCC. Methods: This study was a retrospective study. We reviewed 71 consecutive patients who underwent ER followed by clinical stage I (T1a: MM) ESCC. We compared patients in the radiotherapy group or non-radiotherapy group after ER. Patients of radiotherapy group received radiation within 3 months after ER. All patients underwent regular follow-up. Recurrence, recurrence-free survival, cancer-specific survival, overall survival, and complications were evaluated. Results: There were 34 cases of radiotherapy group and 37 cases of non-radiotherapy group. 3 patients (8.9 %) in the radiotherapy group experienced intraluminal mucosal recurrence, and 2 patients (6.6 %) experienced local recurrence. On the other hand, in the non-radiotherapy group, 9 patients (24.3 %) experienced intraluminal mucosal recurrence, and 7 patients (18.9 %) experienced local recurrence (intraluminal mucosal recurrence: p< 0.05, local recurrence p=0.14). The recurrent group received chemotherapy. The 3-year cumulative recurrence-free survival was 97 % in the radiotherapy group and 83.7 % in the non-radiotherapy group (p< 0.05). No severe radiation toxicities were recorded. Conclusions: The radiotherapy after ESD reduced the risk of lymph nodes recurrence not only local lymph node recurrence but also new intraluminal mucosal recurrence, and safe and effective therapeutic strategy.

Patterns of lymph node metastasis and long-term outcomes of splenic flexure colon cancer: a descriptive study from a Japanese high-volume center.

The pattern of lymph node metastasis and the appropriate extent of lymph node dissection in splenic flexure colon cancer remain unclear. This study aimed to describe the clinical characteristics, lymph node metastasis patterns, and oncological outcomes of patients with splenic flexure colon cancer. The data of patients with splenic flexure cancer diagnosed with pathological stages I-III were extracted from a hospital database. Lymph nodes were mapped and numbered according to the guidelines of the Japanese Society for Cancer of the Colon and Rectum. Five-year disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. Among 151 patients, 37.1% had lymph node metastasis. The proportion of lymph node metastasis were 30.1% at station 221, 5.1% at station 222, 2.8% at station 223, 19.8% at station 231, 2.7% at station 232, and 0% at station 253. Among the 59 patients with an accessory middle colic artery, 19 had lymph node metastasis only at stations 221 (14/47) and 231 (5/47). The 5-year estimated DFS rates were 100% for stage I, 94.4% (95% CI, 83.6-98.2) for stage II, and 79.9% (95% CI, 65.6-88.8) for stage III. Ten patients experienced distant recurrence: liver (n = 5), peritoneum (n = 2), para-aortic lymph node (n = 2), and lung metastasis (n = 1). No local recurrence was observed. In splenic flexure colon cancer, lymph node dissection around the IMA route may be omitted. Similarly, dissection along the left branch of the middle colic artery or the left colic artery may be unnecessary in the presence of an accessory middle colic artery.

Indicators of survival and prognostic factors in women treated for cervical cancer at a tertiary care center in Bangladesh

Background: Cervical cancer remains a major cause of cancer deaths among females in low and middle-income countries. Local survival studies are crucial for assessing overall management effectiveness, as they reflect the level of care provided and awareness among the population about screening and early diagnosis. Objectives: To analyze disease-free survival (DFS) among patients treated for cervical cancer and investigate clinical, management, and outcome-related independent factors associated with survival. Methods: A retrospective study was conducted on 393 cervical cancer patients from January 2014 to 2020 at the Gynecological Oncology Department of the National Institute of Cancer Research and Hospital (NICRH), analyzing demographic and clinical data, tumor characteristics, treatment options, and outcomes, including recurrence, as predictors of survival. Results: Three hundred ninety-three patients included in this study. The mean average age was 49 years, range 28-85 years. Total follow-up times(months), mean 38; range (6-108) months. Among them 61% were postmenopausal, with a majority of women having a parity of 59% and an average marriage age of 14.93±3.95. The most common presenting symptom was irregular bleeding, with 62.8% of patients being illiterate. Tumor characteristics included FIGO stage I, II, and III, with squamous cell carcinoma being the most common histopathological type. Patients received initial surgery (21.6%), radiotherapy (74%), and palliative care (4%). The mean duration of follow-up (DFS) was 2.20 years in <24 months and 3.35 years in >24 months. Residual disease and recurrence were 6.4% and 30.5%, with local recurrence being the most common (22.6%) and liver being the most common site of distal recurrence (38.3%). Survival was independently associated with age, grade II, and FIGO stage III. Conclusion: Age, grade, and FIGO clinical stages adversely affect the overall survival of cervical cancer patients. J Bangladesh Coll Phys Surg 2025; 43: 25-31

Leveraging survival analysis and machine learning for accurate prediction of breast cancer recurrence and metastasis

Breast cancer, with its high incidence and mortality globally, necessitates early prediction of local and distant recurrence to improve treatment outcomes. This study develops and validates predictive models for breast cancer recurrence and metastasis using Recurrence-Free Survival Analysis and machine learning techniques. We merged datasets from the Molecular Taxonomy of Breast Cancer International Consortium, Memorial Sloan Kettering Cancer Center, Duke University, and the SEER program, creating a comprehensive dataset of 272, 252 rows and 23 columns. Our methodology utilized three predictive strategies: assessing recurrence risk, differentiating local from distant recurrences, and identifying potential metastatic sites. Key prognostic factors were identified through survival analysis. LightGBM, XGBoost, and Random Forest models were employed and validated against data from the Baheya Foundation. The models demonstrated strong performance; the survival analysis achieved a C-index of 0.837. The LightGBM model reached an AUC of 92% in predicting recurrences, while XGBoost and Random Forest models distinguished recurrence types with up to 86% accuracy, and they effectively differentiated between bone metastasis and all other locations combined (brain, liver, and lungs). This study highlights the significant potential of machine learning in advancing breast cancer management and sets a new benchmark for predictive analytics. Future research will integrate genetic data to further enhance these models.

Principles of Surgical Treatment of Soft Tissue Sarcomas

Soft tissue sarcoma (STS) is a group of highly heterogeneous tumors of mesenchymal origin that have variable primary site locations and clinical behavior. Despite the broad diversity of STS, the standard of care involves surgical resection with or without radiation therapy (RT) to control local recurrence and systemic treatment in select cases. The complexities of STS require a critical understanding of the preoperative work-up process, surgical treatment, and postoperative management. Advanced imaging plays a vital role in the characterization of the soft tissue mass, preoperative biopsy planning, and disease staging. Surgical treatment prioritizes wide resection with negative margins, supported by newer margin classification systems for better prognosis. Further, advancements in surgical technique have enabled limb-salvage surgery to largely replace amputation in the management of these tumors. Additional surgical considerations, such as nerve preservation, vascular reconstruction, and complex tissue closure, further highlight the complexity of STS management. Lastly, postoperative follow-up is critical for the early detection of local or distant recurrences. For complex cases, such as unplanned excisions or invasive tumors, strategies like re-resection may be beneficial. Ongoing research into imaging, chemotherapy, and targeted therapies will further refine management strategies, especially in complex and recurrent cases. This review highlights the essential aspects of STS surgical management and underscores the need for coordinated, multidisciplinary care to enhance both survival and quality of life for affected patients.

Long-Term Outcomes of Radiation Monotherapy Versus Combined Radiation Monotherapy + Hormone Therapy in Low-Risk Early-Stage Breast Cancer Patients 70 Years or Older After Breast-Conserving Surgery.

Standard therapy for breast cancer after breast-conserving surgery is radiation therapy (RT) plus hormone therapy (HT). For patients with a low-risk of recurrence, there is an interest in deescalating therapy. A retrospective study was carried out for patients treated at the Swedish Cancer Institute from 2000 to 2015, aged 70 years or older, with pT1N0 or pT1NX estrogen receptor-positive and ERBB2-negative unifocal breast cancer without positive surgical margins, high nuclear grade, or lymphovascular invasion. Patient numbers were sufficient to carry out analyses for RT + HT (n = 307) and RT alone (n = 148). The median follow-up was 9.6 years. There were no statistically significant differences in adjusted overall survival (OS), disease-specific death, progression-free survival (PFS), distant recurrence, and second primary cancers with RT monotherapy compared with RT + HT. Cumulative rates of all of these outcomes were <5%, even at 15 years of follow-up, regardless of treatment, greatly outweighed by the incidence of death from other causes in this elderly population. In matched analysis, we calculated a hazard ratio of 1.12 (95% CI, 0.82-1.53) for RT versus RT + HT for OS and a hazard ratio of 1.12 (95% CI, 0.82-1.53) for RT versus RT + HT for PFS. Our data suggest that elderly, low-risk breast cancer patients have similarly high OS and PFS with low rates of local recurrence, distant recurrence, and death from breast cancer with much higher rates of death from competing causes, whether treated with RT or HT + RT. These patients are likely to die of other causes without disease recurrence, regardless of which of these treatments is used. Thus, they may benefit from the administration of more modern forms of breast irradiation without the need for adjuvant systemic hormone therapy. A detailed analysis of which clinical, pathologic, genomic, and comorbidity variables are needed to select these patients.

Prediction of pathological complete response after neoadjuvant chemotherapy for HER2-negative breast cancer patients with routine immunohistochemical markers

BackgroundPathological complete response (pCR) is an established surrogate marker for prognosis in patients with breast cancer (BC) after neoadjuvant chemotherapy. Individualized pCR prediction based on clinical information available at biopsy, particularly immunohistochemical (IHC) markers, may help identify patients who could benefit from preoperative chemotherapy.MethodsData from patients with HER2-negative BC who underwent neoadjuvant chemotherapy from 2002 to 2020 (n = 1166) were used to develop multivariable prediction models to estimate the probability of pCR (pCR-prob). The most precise model identified using cross-validation was implemented in an online calculator and a nomogram. Associations among pCR-prob, prognostic IHC3 distant recurrence and disease-free survival were studied using Cox regression and Kaplan–Meier analyses. The model’s utility was further evaluated in independent external validation cohorts.Results273 patients (23.4%) achieved a pCR. The most precise model had across-validated area under the curve (AUC) of 0.84, sensitivity of 0.82, and specificity of 0.71. External validation yielded AUCs between 0.75 (95% CI, 0.70–0.81) and 0.83 (95% CI, 0.78–0.87). The higher the pCR-prob, the greater the prognostic impact of pCR status (presence/absence): hazard ratios decreased from 0.55 (95% central range, 0.07–1.77) at 0% to 0.20 (0.11–0.31) at 50% pCR-prob. Combining pCR-prob and IHC3 score further improved the precision of disease-free survival prognosis.ConclusionsA pCR prediction model for neoadjuvant therapy decision-making was established. Combining pCR and recurrence prediction allows identification of not only patients who benefit most from neoadjuvant chemotherapy, but also patients with a very unfavorable prognosis for whom alternative treatment strategies should be considered.

The Olive Oil Phenolic S-(-)-Oleocanthal Suppresses Colorectal Cancer Progression and Recurrence by Modulating SMYD2-EZH2 and c-MET Activation

Background/Objectives: Colorectal cancer (CRC) is the third most common cancer in the US and the second leading cancerassociated mortality cause. Available CRC therapies achieve modest outcomes and fail to prevent its recurrence. Epidemiological studies indicated that the Mediterranean diet rich in olive oil reduced CRC incidence. This study aimed at the identification and assessment of active anti-CRC olive phenolics. Methods: The MTT, wound-healing and colony formation assays were used to discover and assess the in vitro anti-CRC activity of olive phenolics. A nude mouse xenografting model was used to assess the in vivo CRC progression and recurrence suppressive activity of OC in pure and crude forms. OC was isolated from olive oil using liquid–liquid extractions. Results: Screening of olive phenolics for in vitro antiproliferative activity against a diverse panel of CRC cell lines identified the extra-virgin olive oil (EVOO) S-(-)-oleocanthal (OC) as the most active hit. OC showed IC50 values of 4.2, 9.8, 14.5, and 4.9 μM against HCT-116, COLO-320DM, WiDr, and SW48 CRC cells, respectively. The lysine methyltransferases SMYD2 and EZH2, along with the receptor tyrosine kinase c-MET proved aberrantly dysregulated in invasive and metastatic CRC. SMYD2 and c-MET were validated as OC molecular targets in multiple malignancies. Daily oral 10 mg/kg OC treatments over 15 days suppressed 72.5% of the KRAS mutant HCT-116-Luc cells tumors weight in male nude mice. Continued OC daily oral use after primary tumor surgical excision over an additional 40 days significantly suppressed the HCT-116-Luc locoregional tumor recurrence and totally prevented the distant tumor recurrence. The SMYD2-EZH2 expressions and c-MET activation were notably suppressed by OC treatments in vitro and in collected animal primary tumors. Conclusions: OC and olive phenolics are potential nutraceutical interventions useful for CRC control and the prevention of its relapse.

Management of Clinically Node-Negative Salivary Gland Cancer: Observation, Neck Dissection, or Neck Irradiation?

Salivary gland malignancies are heterogeneous tumors with highly variable outcomes. Elective neck management options include observation, neck dissection (ND), and neck irradiation (NI). We sought to compare outcomes of cN0 salivary gland cancer by elective neck management. An IRB-approved registry was queried for cN0 salivary gland cancers and categorized based on neck management into observation, ND, NI, and ND + NI groups. cN0 included no evidence of clinical or radiographic metastatic lymphadenopathy. A total of 445 patients were included with 203 in observation, 83 ND, 71 NI, and 88 ND + NI. Median follow-up was 60.8 months (range 0.4-258). There were 47% clinical T1 tumors, 29% T2, and 12% of each T3 and T4. Exactly 90% were cN0 and 10% with borderline lymph node(s). The major salivary gland was the most common site (74%) and the most common histologies included 28% mucoepidermoid and 20% adenoid cystic. Risk factors associated with regional recurrence include age, borderline lymph node features, pathologic T and N stage, poorly differentiated, positive margin, lymphovascular space invasion, and extranodal extension (all p < 0.05). There was no significant difference in local (9.9%-16.7%, p = 0.6) or regional (3.9%-9.4%, p = 0.76) recurrence between all four groups. Five-year distant recurrence was significantly different at 7% for observation, 16% in ND, 25% in NI, and 37% in ND + NI (p < 0.001). Ten-year OS estimates were 78% for observation, 66% for ND, 69% for NI, and 52% in ND + NI (p < 0.001). For patients with cN0 salivary gland cancer, ND and NI yield similar regional control in appropriately selected patients. In high-risk patients with several adverse risk features ND + NI results in favorable regional control but distant metastasis is a driving factor affecting overall survival.

A Novel Nomogram for Estimating a High-Risk Result in the EndoPredict® Test for Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Carcinoma.

Background/Objectives: The EndoPredict® assay has been widely used in recent years to estimate the risk of distant recurrence and the absolute chemotherapy benefit for patients with estrogen (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, there are no well-defined criteria for selecting patients who may benefit from the test. The aim of this study was to develop a novel nomogram to estimate the probability of obtaining a high-risk EndoPredict® result in clinical practice. Methods: The study cohort comprised 348 cases of T1-3/N0-1a/M0 ER-positive/HER2-negative breast carcinoma. A multivariate analysis was conducted using a training cohort (n = 270) based on clinicopathological features that demonstrated a statistically significant correlation with the EndoPredict® result in a univariate analysis. The predictive model was subsequently represented as a nomogram to estimate the probability of obtaining a high-risk result in the EndoPredict® assay. The predictive model was then validated using a separate validation cohort (n = 78). Results: The clinicopathological features incorporated into the nomogram included tumor size, tumor grade, sentinel lymph node status, pN stage, and Ki67. The internal validation of the model yielded an area under the curve (AUC) of 0.803 (95% CI = 0.751, 0.855) in the receiver operating characteristic (ROC) curve for the training cohort, with an optimal sensitivity and specificity at a threshold of 0.536. The external validation yielded an AUC of 0.789 (95% CI = 0.689, 0.890) in its ROC curve, with optimal sensitivity and specificity achieved at a threshold of 0.393. Conclusions: This study presents, for the first time, the development of a clinically accessible nomogram designed to estimate the probability of obtaining a high-risk result in the EndoPredict® assay. The use of easily available clinicopathological features allows for the optimization of patient selection for the EndoPredict® assay, ensuring that those who would most benefit from undergoing the test are identified.

Partial versus radical cystectomy in localized colorectal cancer: a systematic review and meta-analysis.

Locally advanced colorectal tumors frequently invade adjacent organs, particularly the urinary bladder in the sigmoid colon and upper rectum, complicating multivisceral resections. This study compared postoperative outcomes of partial cystectomy (PC) and total cystectomy (TC) in patients with locally advanced colorectal cancer. A systematic review was conducted in PubMed, Scopus, Central Register of Clinical Trials, and Web of Science for studies published up to November 2024. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity was assessed with I2 statistics. Statistical analyses were performed in R Software 4.4.1. Nine retrospective studies including 894 patients were analyzed. Among them, 433 (48.43%) underwent PC, and 461 (51.57%) underwent TC. Compared to TC, PC was associated with significantly lower rates of surgical site infection (OR 0.33; 95% CI 0.13-0.80; p = 0.015), shorter operative time (MD - 169.7min; 95% CI - 214.1 to - 125.3; p < 0.01), reduced blood loss (MD - 1005.9ml; 95% CI - 1362.1 to - 649.8; p < 0.01), and shorter hospital stay (MD - 6.6days; 95% CI - 9.4 to - 3.9; p < 0.01). No significant differences were observed between groups in local or distant recurrence, urinary and intestinal leaks, pelvic abscess, ileus, urinary tract infection, or 90-day mortality. Partial cystectomy demonstrated superior postoperative outcomes, including fewer surgical site infections, reduced operative time, less blood loss, and shorter hospitalization. Oncological outcomes and other postoperative complications were comparable between PC and TC, supporting PC as a safe and effective option in selected patients.