Baseline Tumor Characteristics Research Articles

Retrospective analysis of HAIP therapy in metastatic colorectal cancer: Efficacy, safety, and prognostic factors.

126 Background: HAIP (hepatic arterial infusion pump) therapy is a promising intervention for metastatic colorectal cancer (mCRC) with liver metastases, addressing significant challenges in management and prognosis. It offers targeted treatment to maximize efficacy while minimizing systemic toxicity. We present a retrospective analysis of patients with metastatic colorectal adenocarcinoma treated with HAIP therapy at an academic center and safety net hospital. Methods: Patients with mCRC and hepatic metastasis who received at least one HAIP floxuridine (FUDR) cycle from 2013 to 2023 were included. Baseline data, including demographics, tumor characteristics, and treatment history, were collected pre-HAIP. The main outcome was overall survival (OS) post-pump placement, with secondary outcomes being real-world progression-free survival (rwPFS) and HAIP-related complications. Results: In total, 88 patients were evaluated for inclusion, of whom 63 met inclusion criteria and were included for analysis. The median age of included patients was 46 years (interquartile range (IQR) 41-57) and 54% were male. Prior to HAIP, 38 (60%) of patients received one line of systemic therapy, while 18 (29%) had two. The median OS from HAIP placement was 28.0 months (95% CI 21.9-NR) and median rwPFS was 11.2 months (95% CI 7.1-16.1). Baseline bilirubin, KRAS mutant status, and CEA were associated with OS in the multivariate cox model. The most common complication from HAIP placement was hematoma (n=4, 6.3%), followed by pump infection (n=2, 3.2%). Grade 3 toxicities from FUDR infusion were infrequent, involving alkaline phosphatase (n=6), AST or ALT elevation (n=3), bilirubin increase (n=2), and platelet count decrease (n=1). Conclusions: HAIP treatment is associated with durable responses and few complications, making it well-tolerated by patients. For individuals with colorectal cancer and hepatic metastases, HAIP chemotherapy using FUDR presents a viable and effective treatment option, potentially improving overall outcomes and quality of life. Further prospective and randomized work may establish the role for HAIP in mCRC with liver metastases.

Characteristics and survival of patients with viral versus nonviral associated hepatocellular carcinoma: a multicenter cohort study.

Viral hepatitis B and C are the leading causes of hepatocellular carcinoma (HCC). With obesity, metabolic-related disorders are increasingly associated with a higher incidence of nonviral HCC. This study aimed to investigate the characteristics, tumor features, treatment outcomes, and survival of patients with viral versus nonviral HCC. This multicenter cohort study was conducted at six tertiary care centers. Patients were recruited between February 2007 and June 2022 and follow-up was recorded until death or the study end (July 2023). The patients were divided into viral-related and nonviral HCC groups. We studied baseline patient characteristics, tumor characteristics, treatment, and overall survival (OS). This study included 2233 patients, 1913 patients with viral and 320 patients with nonviral HCC. Patients with nonviral HCC presented with more advanced Barcelona Clinic Liver Cancer (BCLC) stages (BCLC stage C or D were present in 26.3% and 53.8% of patients with viral and nonviral HCC, respectively) that affected the median OS (19.167 vs. 13.830 months, P-value <0.001 for viral and nonviral HCC, respectively). The OS did not differ between patients with viral and nonviral HCC treated with resection, percutaneous ablation, trans-arterial chemoembolization, or Sorafinib. The independent factors affecting the survival of nonviral HCC were albumin-bilirubin score (hazard ratio = 2.323, 95% confidence interval (CI): 1.696-3.181, P-value <0.001), tumor size (hazard ratio = 1.085, 95% CI: 1.019-1.156, P-value 0.011), and alpha-fetoprotein (hazard ratio = 1.000, 95% CI: 1.000-1.000, P-value 0.042). Patients with nonviral HCC had higher BMI, worse performance status, BCLC stage, and tumor response than those with viral HCC.

Immigrant Health and Early-Onset Colorectal Cancer Disparities: Results From the Spanish Early-Onset Colorectal Cancer Consortium.

To better understand immigration disparities among a Spanish Early-Onset Colorectal Cancer (SECOC) subset, according to the country of origin. We selected 250 consecutive participants from the SECOC consortium. Data on baseline patient and tumor characteristics, family history of colorectal cancer (CRC), and follow-up were collected. The presence of mismatch repair deficiency was also assessed. Special data regarding country of origin, time of stay in Spain in case of other different country, and a 10-year cutoff that specifies the obtaining of Spanish nationality defined the variables of interest for comparison. Seventy-five percent of patients with early-onset CRC (EOCRC) (188) were born in Spain, whereas the other 25% were born outside of Spain. The mean time of living in Spain until the EOCRC diagnosis was 16.5 years. Comparatively, most of the analyzed features showed equivalent proportions between cohorts. Only Spanish patients appeared to have more familial cancer component in first degree in general (32.3%; P = .01), compared with non-Spaniards, which showed a predominant sporadic component (56.4%; P < .001). Among immigrants, those patients living in Spain before CRC diagnosis ≤10 years were younger at diagnosis (39.1 v 42.5), more frequently male (77.8 v 47.7), were in more advanced stages (88.8% diagnosed at stage III and IV [P = .01]), and had a worse prognosis regarding recurrence rates (29.4% v 6.3%). Although there were few differences between Spanish and non-Spanish EOCRC, the most remarkable difference was that linked with the situation of those immigrants who have recently arrived in Spain, in relation to their lower health coverage, which could be associated with the delay in the diagnosis and their subsequent worse prognosis.

Safety and Postoperative Outcomes of Transoral Surgery for Oropharyngeal Carcinoma in Older Adults

Transoral surgery (TOS) has become the primary surgical treatment for oropharyngeal squamous cell carcinoma (OPSCC). However, despite the increasing incidence of OPSCC in older patients, data regarding the safety and postoperative outcomes of TOS in this subgroup are lacking. This study aimed to evaluate the safety and postoperative outcomes of TOS in patients with OPSCC aged 70 years or older compared with younger individuals. This retrospective cohort study included patients with microscopic diagnostic confirmation of invasive OPSCC diagnosed between 2010 and 2021. Data were obtained from the US National Cancer Database. Data were analyzed in March 2024. Minimally invasive TOS not converted to an open approach. Multivariable logistic and linear regression models were constructed to compare postoperative outcomes, adjusting for baseline patient and tumor characteristics. The results are reported as odds ratios (ORs) or mean differences with corresponding 95% CI, as appropriate. A total of 10 430 patients (mean [SD] age, 60.7 [9.6] years; 8744 [83.8%] male) were included, with 1808 patients (17.3%) aged at least 70 years. No clinically meaningful difference was observed in terms of postoperative mortality at 30 days (adjusted OR, 1.24; 95% CI, 0.65-2.33) or 90 days (adjusted OR, 1.11; 95% CI, 0.65-1.87). Patients aged 70 years or older were less likely to undergo adjuvant radiotherapy (adjusted OR, 0.69; 95% CI, 0.57-0.83) and chemotherapy (adjusted OR, 0.63; 95% CI, 0.51-0.77). In addition, the adjuvant treatment was more frequently not administered in the older population due to patient refusal or comorbidities, despite being clinically indicated (radiotherapy: adjusted OR, 1.36; 95% CI, 1.05-1.77; chemotherapy: adjusted OR, 1.70; 95% CI, 1.17-2.45). No meaningful differences were observed regarding the remaining study outcomes, apart from a slightly longer hospitalization time for older patients, with an adjusted mean difference of 0.39 (95% CI, 0.05-0.74) days. Findings from this study suggest that age was not independently associated with postoperative mortality in older patients undergoing TOS for OPSCC. However, older patients less frequently received adjuvant radiotherapy and chemotherapy compared with younger patients, and future studies should be conducted to examine the impact on long-term survival.

Chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: Pooled analysis of the CAO/ARO/AIO-12 and the OPRA randomized phase 2 trials

Total neoadjuvant therapy (TNT) has been used for patients with locally advanced rectal cancer. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy (CT) is a matter of debate. We performed a pooled analysis of the CAO/ARO/AIO-12 and OPRA multicenter, randomized phase 2 trials to identify patient subsets that could benefit from one TNT sequence over the other regarding disease-free survival (DFS). Patients with stage II/III rectal cancer were randomized to CRT (50.4-54Gy) with either induction (INCT-CRT) or consolidation CT (CRT-CNCT) with fluorouracil, leucovorin, oxaliplatin (CAO/ARO/AIO-12 and OPRA) or capecitabine and oxaliplatin (OPRA) followed by mandatory total mesorectal excision (TME) (CAO/ARO/AIO-12) or selective watch-and-wait surveillance (OPRA). 311 and 324 patients were recruited from June 15, 2015 to January 31, 2018; and from April 12, 2014 to March 30, 2020 in the two trials, respectively. Pretreatment clinical and tumor characteristics included were age, sex, ECOG, cT-category, cN-category, clinical UICC stage, location from anal verge, and tumor grade. In total, 628 eligible patients were included in the pooled analysis (CAO/ARO/AIO-12, n=304; OPRA, n=324). Of those, 313 were randomly assigned to the INCT-CRT group, and 315 to the CRT-CNCT group. Median follow-up was 43 months (IQR, 35-49) months in the CAO/ARO/AIO-12 trial and 61,2 months (IQR, 42-68,4) in the OPRA trial. Pooled analysis of baseline clinical and tumor characteristics did not identify any subgroups of patients that would benefit by the one TNT sequence over the other with regard to DFS. To our knowledge, this is the first pooled analysis of two randomized trials after direct head-to-head comparison of both TNT sequences. Both trials reported higher rates of complete response with CRT-CNCT, and this should be considered the preferred TNT sequence if organ preservation is a priority.

Racial and ethnic disparities in mortality among World Trade Center Health Registry enrollees with post-9/11 cancer.

There are well-documented racial and ethnic disparities in mortality after cancer in the general population, but less is known about whether disparities also exist in disaster-exposed populations. We conducted a longitudinal cohort study of 4341 enrollees in the World Trade Center Health Registry (WTCHR) with a first-ever primary invasive cancer diagnosis after 9/11/2001 and followed through 2020. We examined associations of race and ethnicity with all-cause mortality risk and cause-specific mortality risk using multivariable Cox proportional hazards regression models and Fine and Gray's proportional sub-distribution hazards models, respectively. Models were adjusted for baseline characteristics and tumor characteristics. We also examined models further adjusted for socioeconomic status (SES), and we used inverse odds weighting to formally test for mediation by SES. Compared to non-Hispanic White enrollees with cancer, non-Hispanic Blacks had higher risks for all-cause mortality (adjusted hazard ratio (aHR) = 1.20, 95% CI = 1.02-1.41) and non-cancer mortality (aHR = 1.48, 95% CI = 1.09-2.01) in the full model. In the model without SES, Hispanic enrollees with cancer had higher risks for all-cause mortality (aHR = 1.32, 95% CI = 1.09-1.60) and cancer mortality (aHR = 1.31, 95% CI = 1.05-1.64) compared to non-Hispanic Whites; these associations became not statistically significant in the full model. In the inverse odds weighting analysis, SES explained 24% and 29% of the disparity in all-cause mortality risk observed in non-Hispanic Blacks and Hispanics, respectively, compared to non-Hispanic Whites. This study found that there are racial and ethnic disparities in mortality after cancer in the WTCHR. Additional studies are needed to further explore the factors mediating these disparities.

Comparison of EPIC Versus HIPEC in the Treatment of Colorectal Peritoneal Metastases and Appendix Tumors Using Inverse Probability of Treatment Weighting.

The selection of hyperthermic intraperitoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) for peritoneal metastases from colorectal cancer or appendiceal neoplasms following cytoreductive surgery (CRS) depends on the surgeon's discretion. This study was designed to compare postoperative and oncologic outcomes of HIPEC and EPIC using inverse probability of treatment weighting (IPTW). This study included 175 patients who received HIPEC or EPIC following CRS at a single tertiary university hospital between December 1999 and December 2020. Inverse probability of treatment weighting analysis was performed to control for pretreatment characteristics between the two groups. Multivariate analysis was performed to determine factors associated with postoperative and survival outcomes. After IPTW, no significant differences in baseline demographics and tumor characteristics were observed between the two groups. The HIPEC group had a significantly longer operation time than the EPIC group. The EPIC group showed a significantly higher postoperative mortality rate than the HIPEC group. Operation time (odds ratio [OR] 1.01; 95% confidence interval [CI] 1.01-1.02; p < 0.001), bowel anastomosis (OR 7.25; 95% CI 1.16-45.2; p = 0.034), neoadjuvant chemotherapy (OR 7.62; 95% CI 1.85-31.4; p = 0.005), and EPIC (OR 8.76; 95% CI 2.16-35.5; p = 0.002) were independent risk factors for major surgical complications. No association was observed between intraperitoneal chemotherapy type and major hematologic toxicity, overall survival, progression-free survival, or peritoneal progression-free survival. EPIC was a risk factor for major surgical complications. Survival outcomes were similar between the two types of intraperitoneal chemotherapy.

Electronic Health Record–Based Nudge Intervention and Axillary Surgery in Older Women With Breast Cancer

Choosing Wisely recommendations advocate against routine use of axillary staging in older women with early-stage, clinically node-negative (cN0), hormone receptor-positive (HR+), and HER2-negative breast cancer. However, rates of sentinel lymph node biopsy (SLNB) in this population remain persistently high. To evaluate whether an electronic health record (EHR)-based nudge intervention targeting surgeons in their first outpatient visit with patients meeting Choosing Wisely criteria decreases rates of SLNB. This nonrandomized controlled trial was a hybrid type 1 effectiveness-implementation study with subsequent postintervention semistructured interviews and lasted from October 2021 to October 2023. Data came from EHRs at 8 outpatient clinics within an integrated health care system; participants included 7 breast surgical oncologists. Data were collected for female patients meeting Choosing Wisely criteria for omission of SLNB (aged ≥70 years with cT1 and cT2, cN0, HR+/HER2- breast cancer). The study included a 12-month preintervention control period; baseline surveys assessing perceived acceptability, appropriateness, and feasibility of the designed intervention; and a 12-month intervention period. A column nudge was embedded into the surgeon's schedule in the EHR identifying patients meeting Choosing Wisely criteria for potential SLNB omission. The primary outcome was rate of SLNB following nudge deployment into the EHR. Similar baseline demographic and tumor characteristics were observed before (control period, n = 194) and after (intervention period, n = 193) nudge deployment. Patients in both the control and intervention period had a median (IQR) age of 75 (72-79) years. Compared with the control period, unadjusted rates of SLNB decreased by 23.1 percentage points (46.9% SLNB rate prenudge to 23.8% after; 95% CI, -32.9 to -13.8) in the intervention period. An interrupted time series model showed a reduction in the rate of SLNB following nudge deployment (adjusted odds ratio, 0.26; 95% CI, 0.07 to 0.90; P = .03). The participating surgeons scored the intervention highly on acceptability, appropriateness, and feasibility. Dominant themes from semistructured interviews indicated that the intervention helped remind the surgeons of potential Choosing Wisely applicability without the need for additional clicks or actions on the day of the patient visit, which facilitated use. This study showed that a nudge intervention in the EHR significantly decreased low-value axillary surgery in older women with early-stage, cN0, HR+/HER2- breast cancer. This user-friendly and easily implementable EHR-based intervention could be a beneficial approach for decreasing low-value care in other practice settings or patient populations. ClinicalTrials.gov Identifier: NCT06006910.

Regional Differences in Stage III Nonseminoma Germ Cell Tumor Patients Across SEER Registries

PurposeWe investigated regional differences in patients with stage III nonseminoma germ cell tumor (NSGCT). Specifically, we investigated differences in baseline patient, tumor characteristics and treatment characteristics, as well as cancer-specific mortality (CSM) across different regions of the United States. MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), patient (age, race/ethnicity), tumor (International Germ Cell Cancer Collaborative Group [IGCCCG] prognostic groups) and treatment (systemic therapy and retroperitoneal lymph dissection [RPLND] status) characteristics were tabulated for stage III NSGCT patients, according to 12 SEER registries representing different geographic regions. Multinomial regression models and multivariable Cox regression models testing for cancer-specific mortality (CSM) were used. ResultsIn 3,174 stage III NSGCT patients, registry-specific patient counts ranged from 51 (1.5%) to 1630 (51.3%). Differences across registries existed for age (12%-31% for age 40+), race/ethnicity (5%-73% for others than non-Hispanic whites), IGCCCG prognostic groups (24%-43% vs. 14-24% vs. 3%-20%, in respectively poor vs. intermediate vs. good prognosis), systemic therapy (87%-96%) and RPLND status (12%-35%). After adjustment, clinically meaningful inter-registry differences remained for systemic therapy (84%-97%) and RPLND (11%-32%). Unadjusted 5-year CSM rates ranged from 7.1% to 23.3%. Finally in multivariable analyses addressing CSM, 2 registries exhibited more favorable outcomes than SEER registry of reference (SEER Registry 12): SEER Registry 4 (Hazard Ratio (HR): 0.36) and SEER Registry 9 (HR: 0.64; both P = .004). ConclusionWe identified important regional differences in patient, tumor and treatment characteristics, as well as CSM which may be indicative of regional differences in quality of care or expertise in stage III NGSCT management.

Predictors of lymph node metastasis and survival in radically resected rectal neuroendocrine tumors: A Surveillance, Epidemiology, and End Results (SEER) database analysis

BackgroundRectal neuroendocrine tumors are uncommon tumor types. Lymph node metastases may occur in up to 40%, potentially impacting decision-making. We aimed to assess risk factors for lymph node metastases of rectal neuroendocrine tumors and their association with overall and cancer-specific survival. MethodsThis retrospective case–control study involved patients with stage I to III rectal neuroendocrine tumors who underwent radical resection. Data were derived from the Surveillance, Epidemiology, and End Results database (2000–2020). Patients with pathologic evidence of lymph node metastases were compared to those without lymph node metastases for baseline patient and tumor characteristics. The main outcomes were lymph node metastases, overall survival, and cancer-specific survival. ResultsIn total, 580 patients (50.9% male; mean age: 58.9 years) were included. The lymph node metastases rate was 37.1%. Independent predictors of lymph node metastases were Grade 2 neuroendocrine tumors (odds ratio: 8.06; P = .001), neuroendocrine carcinoma (odds ratio: 2.59, P = .006), large-cell neuroendocrine carcinoma (odds ratio: 4.89; P = .017), T2 tumors (odds ratio: 6.44; P < .001), T3 tumors (odds ratio: 27.5; P < .001), and T4 tumors (odds ratio: 17.3; P < .001). Lymph node metastases were associated with shorter restricted mean overall survival (40.8 vs 52.7 months; P < .001) and cancer-specific survival (41.3 vs 54.8 months; P < .001). When adjusted for other confounders, the nodal status of rectal neuroendocrine tumors was not independently associated with overall (hazard ratio = 1.56; P = .165) or cancer-specific survival (hazard ratio = 1.69; P = .158). Significant factors associated with worse overall survival and cancer-specific survival were age, tumor size, neuroendocrine carcinomas, large-cell neuroendocrine carcinomas, and the number of positive lymph nodes. ConclusionsLymph node metastases of rectal neuroendocrine tumors were more likely associated with high-grade, large-sized, and T2 to T4 tumors. The number of involved lymph nodes was an independent predictor of overall and cancer-specific survival. Other independent survival predictors were tumor grade, size, and T stage.

A retrospective cohort study of intra-corporeal versus extra-corporeal anastomosis for right hemicolectomy with cost-effectiveness analysis.

We aimed to compare outcomes and cost effectiveness of extra-corporeal anastomosis (ECA) versus intra-corporeal anastomosis (ICA) for laparoscopic right hemicolectomy using the National Surgical Quality Improvement Programme data. Patients who underwent elective laparoscopic right hemicolectomy for colon cancer from January 2018 to December 2022 were identified. Non-cancer diagnoses, emergency procedures or synchronous resection of other organs were excluded. Surgical characteristics, peri-operative outcomes, long-term survival and hospitalisation costs were compared. Incremental cost-effectiveness ratio (ICER) was used to evaluate cost-effectiveness. A total of 223 patients (175 ECA, 48 ICA) were included in the analysis. Both cohorts exhibited comparable baseline patient, comorbidity, and tumour characteristics. Distribution of pathological TMN stage, tumour largest dimension, total lymph node harvest and resection margin lengths were statistically similar. ICA was associated with a longer median operative duration compared with ECA (255 min vs. 220 min, P < 0.001). There was a quicker time to gastrointestinal recovery, with a shorter median hospital stay in the ICA group (4.0 versus 5.0 days, P = 0.001). Overall complication rates were comparable. ICA was associated with a higher surgical procedure cost (£6301.57 versus £4998.52, P < 0.001), but lower costs for ward accommodation (£1679.05 versus £2420.15, P = 0.001) and treatment (£3774.55 versus £4895.14, P = 0.009), with a 4.5% reduced overall cost compared with ECA. The ICER of -£3323.58 showed ICA to be more cost effective than ECA, across a range of willingness-to-pay thresholds. ICA in laparoscopic right hemicolectomy is associated with quicker post-operative recovery and may be more cost effective compared with ECA, despite increased operative costs.

Irreversible Electroporation as a Valid Treatment Option for Hepatic Epithelioid Hemangioendothelioma: An International Multicenter Experience

PurposeHepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor with currently no established standard of care. This international multicenter retrospective study assesses the use of percutaneous irreversible electroporation (IRE) as an ablative tool to treat HEHE and provides a clinical overview of the current management and role of IRE in HEHE treatment.Material and MethodsBetween 2017 and 2023, 14 patients with 47 HEHE tumors were treated with percutaneous IRE using CT-scan guidance in 23 procedures. Baseline patient and tumor characteristics were evaluated. Primary outcome measures included safety and effectiveness, analyzed using Common Terminology Criteria for Adverse Events (CTCAE) and treatment response by mRECIST criteria. Secondary outcome measures included technical success, post-treatment tumor sizes and length of hospital stay. Technical success was defined as complete ablation with an adequate ablative margin (intentional tumor free ablation margin > 5 mm).ResultsIRE treatment resulted in technical success in all tumors. Following a median follow-up of 15 months, 30 tumors demonstrated a complete response according to mRECIST criteria. The average tumor size pre-treatment was 25.8 mm, accompanied by an average reduction in tumor size by 7.5 mm. In 38 out of 47 tumors, there was no evidence of local recurrence. In nine tumors, residual tumor was present. There were no cases of progressive disease. Median length of hospital stay was one day. Only one grade 3 CTCAE event occurred, a pneumothorax requiring chest tube placement.ConclusionThe current study provides evidence that IRE is a safe and efficacious minimally invasive treatment option for HEHE.Graphical

Partial nephrectomy after a period of active surveillance: Are perioperative and pathology outcomes worsened compared to immediate surgery?

IntroductionActive surveillance (AS) is a viable strategy for managing small renal masses (SRMs) in lieu of immediate surgery, but concerns persist regarding its impact on delayed partial nephrectomy (PN) outcomes. We aimed to compare perioperative and pathological outcomes of patients initially on AS for SRMs, later undergoing PN, against those undergoing immediate PN. Materials and methodsData were extracted from a prospective institutional database (January 2018–September 2023) for patients with cT1a renal masses. Only malignancies confirmed at final pathology were included. Baseline patient and tumor characteristics and the time from AS enrollment to PN were recorded. Surgical, renal functional, and final pathology outcomes were analyzed, including histology, tumor size, pT stage, upstaging rate, and positive surgical margins. Predictors of upstaging were identified using logistic regression models. ResultsAnalysis included 356 patients: 307 immediate PN and 49 deferred PN after a median of 18 months in AS. Groups had comparable baseline characteristics; no significant differences emerged in surgical and postoperative outcomes. Final pathology revealed no significant disparities in tumor size, histology, positive margins, or upstaging, though pT stage distribution differed (2.4 % versus 4.3 % for pT3a, immediate versus deferred, p = 0.04). Univariable analysis identified RENAL Score (OR 1.29, 95 % C.I. 1.09–1.53, p = 0.003) and clinical tumor size (OR 1.16, 95 % C.I. 1.10–1.22, p < 0.01) as upstaging predictors, confirmed by multivariable analysis (p < 0.01). ConclusionOur comparative analysis found no worsened perioperative or adverse pathological outcomes in patients with deferred PN, supporting the safety of this approach in managing SRMs, at least as an initial option.

Development of a novel risk stratification model for immune-related adverse events for patients with advanced melanoma and non-small cell lung cancer treated with immune checkpoint inhibitors.

2649 Background: Immune checkpoint inhibitors (ICI) transformed treatment paradigm across cancers. There remain few reliable, clinically accessible predictors of ICI-induced immune related adverse events (irAEs). We derive a novel risk stratification model for irAEs using baseline patient, tumor and treatment variables in a large cohort of patients with advanced melanoma (AM) or non-small cell lung cancer (NSCLC) treated with ICI. Methods: We conducted a multi-centre retrospective observational cohort study of consecutive patients with AM or NSCLC receiving ≥ 1 cycle of single-agent or combination ICI, in any line, 2015 - 2023, in Alberta, Canada. Clinically significant irAEs, defined as those requiring treatment delay or systemic steroids/steroid sparing agents, were identified as outcome of interest. The association between irAEs, overall survival (OS), and time to next treatment (TTNT) was assessed with Cox Proportional Hazards regression. Stepwise logistic regression was used to select and weight baseline variables associated with development of irAEs to derive a predictive risk score. Model validation was carried out on 500 iterations of bootstrapped samples. Harrel’s C-index was calculated and internally validated to ascertain the model’s discriminatory performance. Results: 1,292 total patients were included, 519 (218/489 [44.6%] AM and 301/803 [37.5%] NSCLC) developing a clinically significant irAE. Using a subset of 801 patients with available baseline characteristics, the following variables were identified and weighted for creation of risk model (risk score attributed): tumor type (NSCLC) (+1), age &gt;60 (+1), ECOG ≥1 (-1), BMI ≥ 25 (+1), ICI after first line (-1), combination ICI (+4), &gt;10 cycles of ICI (+2), albumin level &lt; LLN (+2), adrenal metastasis (+1), multiple sites of metastasis (-1). Patients were stratified into 3 irAE risk groups based on combined score: low (n = 230, risk score ≤ 0), intermediate (n = 412, risk score 1-2), high (n = 159, risk score ≥3). The risk model performed well with an optimism-corrected c-index of 0.707 in internal validation, and strong association with odds of irAE occurrence (Table). The development of irAE was associated with an improvement in OS (HR 0.48, 95% CI 0.41-0.44, p&lt;0.001), with a median OS of 34.3 (95% CI 28.8-39.6) months compared to 12.0 (95% CI 10.6-14.3) months for those who did not develop an irAE. Similar robust stratification was also seen with TTNT. Conclusions: We presented and internally validated, a simple risk stratification tool that utilizes readily available baseline patient, tumor, and treatment characteristics to robustly stratify risk of irAE development. [Table: see text]

Clinical behavior of breast cancer in young BRCA carriers and prognostic impact of the timing of genetic testing: Results from an international cohort study.

10503 Background: Germline BRCA testing is recommended in all patients (pts) diagnosed with breast cancer (BC) at a young age (40 years or younger). Limited evidence exists regarding clinical behavior of BC in young BRCA1and BRCA2 carriers or the impact of the timing of genetic testing (before or at diagnosis) on tumor characteristics and pts outcomes. Methods: This was an international, multicenter, hospital-based, retrospective cohort study including pts harboring germline pathogenic variants (PVs) in BRCA1or BRCA2 and diagnosed with stage I-III invasive BC at 40 years or younger between January 2000 and December 2020 (NCT03673306). Baseline pt, tumor, and treatment characteristics, as well as survival outcomes (disease-free survival [DFS] and overall survival [OS]) were compared between BRCA1and BRCA2carriers. A further comparison was performed between pts who underwent genetic testing before (i.e. any time up to 2 months prior to BC diagnosis) or at (i.e. between 2 months prior and up to 6 months after diagnosis) BC diagnosis. Results: From 78 centers worldwide, 4,752 pts were included, of whom 3069 harbored BRCA1and 1683 BRCA2 PVs. Compared to BRCA2carriers, BRCA1 carriers were significantly younger, had more grade 3 tumors, less nodal involvement, lobular histology, hormone receptor and HER2 positivity, and received chemotherapy more frequently and endocrine therapy less frequently. Median follow-up was 7.8 years (range 4.4-12.6 years). Second primary BCs (13.7% vs. 9.3%) and non-breast new primary malignancies (4.5% vs. 3.0%) were significantly more frequent among BRCA1 carriers, while distant recurrences were less frequent (9.7% vs. 13.6%). No differences in DFS or OS were observed between BRCA1 and BRCA2 carriers. However, BRCA1 carriers had worse DFS and OS in the first 5 years due to a peak in DFS events in the first 2 years while BRCA2 carriers had a constant risk of recurrence over time and worse OS after year 9. Compared to pts tested for BRCA at BC diagnosis (n = 1671), those tested before BC diagnosis (n = 411) had significantly smaller tumors (T1: 61.3% vs 32.4%) and less nodal involvement (N0: 65.9% vs 50.8%). 8-year DFS and OS in patients tested before and at BC diagnosis were 73% vs 70% (HR 1.25; 95% CI 0.99-1.58) and 91% vs 87% (HR 1.65; 95% CI 1.08-2.52), respectively. Conclusions: In this global study of young BRCA carriers, different pts, tumor, and treatment characteristics, as well as pattern and risk of DFS/OS events over time were observed between BRCA1and BRCA2. Identification of carrying a BRCA PV in healthy individuals led to earlier BC diagnosis and improved OS. These findings highlight the importance of conducting efforts to identify women at risk for carrying a BRCA1or BRCA2PV to offer them genetic counseling and testing to inform not only prevention, but tailored earlier detection, treatment and follow-up strategies once diagnosed.

Time-varying associations of patient and tumor characteristics with cancer survival: an analysis of SEER data across 14 cancer sites, 2004-2017.

Surveillance, Epidemiology, and End Results (SEER) cancer registries provides information about survival duration and cause of death for cancer patients. Baseline demographic and tumor characteristics such as age, sex, race, year of diagnosis, and tumor stage can inform the expected survival time of patients, but their associations with survival may not be constant over the post-diagnosis period. Using SEER data, we examined if there were time-varying associations of patient and tumor characteristics on survival, and we assessed how these relationships differed across 14 cancer sites. Standard Cox proportional hazards models were extended to allow for time-varying associations and incorporated into a competing-risks framework, separately modeling cancer-specific and other-cause deaths. For each cancer site and for each of the five factors, we estimated the relative hazard ratio and absolute hazard over time in the presence of competing risks. Our comprehensive consideration of patient and tumor characteristics when estimating time-varying hazards showed that the associations of age, tumor stage at diagnosis, and race/ethnicity with risk of death (cancer-specific and other-cause) change over time for many cancers; characteristics of sex and year of diagnosis exhibit some time-varying patterns as well. Stage at diagnosis had the largest associations with survival. These findings suggest that proportional hazards assumptions are often violated when examining patient characteristics on cancer survival post-diagnosis. We discuss several interesting results where the relative hazards are time-varying and suggest possible interpretations. Based on the time-varying associations of several important covariates on survival after cancer diagnosis using a pan-cancer approach, the likelihood of the proportional hazards assumption being met or corresponding interpretation should be considered in survival analyses, as flawed inference may have implications for cancer care and policy.

Overall Survival in Patients with Esophageal Cancer and Clinical Complete Response after Radio Chemotherapy: Should a Watchful Waiting Strategy be the new Standard of Care?

Abstract Background The current standard of care for curative treatment of esophageal cancer (EC) consists of neoadjuvant radio chemotherapy (RCT) followed by resection. However, an organ-sparing approach with a watchful waiting (WW) strategy and resection only in case of cancer recurrence is gaining importance in patients with clinical complete response (cCR) after RCT. Nevertheless, data on overall survival, particularly in subgroups with and without tumor recurrence, is limited. Aims To compare overall survival (OS) rates in patients with cCR based on initial management and at time of recurrence. Methods We retrospectively analyzed data from all patients with EC and cCR to RCT between 01/2014 and 12/2021. OS- and disease-free survival was calculated using Kaplan-Meier survival analysis. Results Of 96 patients with cCR after RCT, 45 underwent resection (47%), and 51 (53%) a WW approach. There were no significant differences in baseline patient or tumor characteristics. In the WW group, 28 patients (55%) had cancer recurrence. Of those, 11 patients (of 28, 39%) underwent either salvage esophagectomy or endoscopic submucosal dissection in curative intent. No significant difference in OS could be detected in patients with WW and either no recurrence or recurrence treated in curative intention (p=0.716). Further, OS was significantly longer in those patients than in patients with primary resection (p=0.031) and WW patients with recurrence and palliative treatment (p&amp;lt;0.001). (Fig 1). Conclusion In a WW concept for patients with EC and cCR after RCT, patients with cancer recurrence can achieve the same OS as patients without recurrence if treated in curative intention. Moreover, OS in both those patient groups was superior to that of patients undergoing direct resection after RCT, supporting a WW approach as at least safe and applicable in clinical practice. Further prospective data are needed to determine the value of WW as standard of care for patients with cCR following neoadjuvant RCT.

Prediction of cognitive decline in older breast cancer survivors: the Thinking and Living with Cancer study.

Cancer survivors commonly report cognitive declines after cancer therapy. Due to the complex etiology of cancer-related cognitive decline (CRCD), predicting who will be at risk of CRCD remains a clinical challenge. We developed a model to predict breast cancer survivors who would experience CRCD after systematic treatment. We used the Thinking and Living with Cancer study, a large ongoing multisite prospective study of older breast cancer survivors with complete assessments pre-systemic therapy, 12 months and 24 months after initiation of systemic therapy. Cognition was measured using neuropsychological testing of attention, processing speed, and executive function (APE). CRCD was defined as a 0.25 SD (of observed changes from baseline to 12 months in matched controls) decline or greater in APE score from baseline to 12 months (transient) or persistent as a decline 0.25 SD or greater sustained to 24 months. We used machine learning approaches to predict CRCD using baseline demographics, tumor characteristics and treatment, genotypes, comorbidity, and self-reported physical, psychosocial, and cognitive function. Thirty-two percent of survivors had transient cognitive decline, and 41% of these women experienced persistent decline. Prediction of CRCD was good: yielding an area under the curve of 0.75 and 0.79 for transient and persistent decline, respectively. Variables most informative in predicting CRCD included apolipoprotein E4 positivity, tumor HER2 positivity, obesity, cardiovascular comorbidities, more prescription medications, and higher baseline APE score. Our proof-of-concept tool demonstrates our prediction models are potentially useful to predict risk of CRCD. Future research is needed to validate this approach for predicting CRCD in routine practice settings.

Evaluation of AJCC staging system and proposal of a novel stage grouping system in retroperitoneal liposarcoma: the Fudan Zhongshan experience.

Overall survival (OS) varies significantly among individuals with heterogeneous retroperitoneal liposarcoma (RPLS), even among those with the same clinical stage. Improved staging of RPLS is a critical unmet need, given the disappointing results of external validations of the 8th American Joint Committee on Cancer (AJCC) TNM staging system. The cohort study included 220 consecutive patients who underwent surgical resection for primary RPLS at the largest sarcoma centre of Fudan University in China from September 2009 to August 2021, combined with 277 adult patients with RPLS in the SEER database from 1975 to 2020. Data analysis was performed from December 2021 to December 2022. Patients were retrospectively restaged according to the 8th and 7th editions of the TNM staging system as well as the new TNM (nTNM) staging system. The primary endpoint was overall survival (OS). Comparative analysis of postoperative survival was performed using the Kaplan-Meier method, and differences between subgroups were tested using the log-rank test. The OS prediction nomogram was generated based on baseline variables and tumour characteristics. Harrell's consistency index (C-index), area under the curve (AUC) of receiver operating characteristic curves (ROC), and calibration curves were used to evaluate the performance of the nomogram. A total of 497 patients were enrolled in the study, including 282 (56.7%) male patients. The median follow-up was 51 months (interquartile range, IQR, 23-83), and the OS rates at 1, 3, and 5 years were 87.9%, 75.3%, and 64.9%, respectively. According to the staging distribution of the AJCC 7th edition, 6 patients were stage IA (1.2%), 189 patients were stage IB (38%), 12 patients were stage IIA (2.4%), 150 patients were stage IIB (30.1%), 131 patients were stage III (26.3%), and 9 patients were stage IV (1.8%). With the 8th edition staging, this distribution changed: 6 patients (1.2%) were stage IA, 189 patients (38%) were stage IB, 12 patients (2.4%) were stage II, 24 patients (4.8%) were stage IIIA, 257 patients (51.7%) were stage IIIB, and 9 patients (1.8%) were stage IV. 182 patients (36.6%) were reclassified according to the nTNM staging system with the new T stage classification. The C-index and log-rank score improved after implementation of nTNM implementation. The nTNM system was associated with improved identification of high-risk patients compared with the AJCC 7th and 8th TNM. The FNCLCC stage proved to be highly prognostic with significant intergroup differences in OS. The calibration curve shows a high degree of agreement between the actual OS rate and the nomogram estimated OS rate. Compared with 8th AJCC TNM, 7th AJCC TNM staging system showed a more homogeneous staging distribution and a slight improvement in the prognostic accuracy of RPLS. The revised T-stage and nTNM systems showed better risk stratification performance. The FNCLCC stage was found to have high prognostic value, further emphasising histological grade is the least negligible prognostic factor in predicting patient survival. The constructed nomogram model enables individualized prognostic analysis and helps to develop risk-adapted therapy for RPLS patients.

Impact of nasogastric tube exclusion after minimally invasive esophagectomy for esophageal cancer: a single-center retrospective study in India.

This study examines the impacts of omitting nasogastric tube (NGT) placement following cervical esophagogastric anastomosis (CEGA) in Enhanced Recovery After Surgery (ERAS) protocols, comparing outcomes to those from early NGT removal. In a retrospective cohort of esophagectomy patients treated for esophageal cancer, participants were divided into two groups: group 1 had the NGT inserted post-CEGA and removed by postoperative day 3, while group 2 underwent the procedure without NGT placement. We primarily investigated anastomotic leak rates, also analyzing hospital stay duration, pulmonary complications, and NGT reinsertion. Among 50 esophageal squamous cell carcinoma patients, 30 in group I were compared with 20 in group II. The baseline demographic and tumor characteristics were similar between both groups. The overall incidence of anastomotic leak was 14.0%, comparable in both groups (16.7% vs. 10.0%, p = 0.63). The postoperative hospital stay was significantly shorter in the no NGT group (median of 7 days vs. 6 days, p = 0.03) with similar major morbidity (Clavien-Dindo grade ≥IIIa; 13.3% vs. 5.0%, p = 0.63). There was no 30-day mortality, and one patient in each group had reinsertion of NGT for conduit dilatation. The exclusion of an NGT across CEGA after esophagectomy did not influence the anastomotic leak rate with comparable complications and a shorter hospital stay.