Principles of risk assessment in colon cancer: immunity is key.

In clinical practice, the administration of adjuvant chemotherapy (ACT) following tumor surgical resection raises a critical dilemma for stage II colon cancer (CC) patients. The prognostic features used to identify high-risk CC patients rely on the pathological assessment of tumor cells. Currently, these factors are considered for stratifying patients who may benefit from ACT at early CC stages. However, the extent to which these factors predict clinical outcomes (i.e. recurrence, survival) remains highly controversial, also uncertainty persists regarding patients' response to treatment, necessitating further investigation. Therefore, an imperious need is to explore novel biomarkers that can reliably stratify patients at risk, to optimize adjuvant treatment decisions. Recently, we evaluated the prognostic and predictive value of Immunoscore (IS), an immune digital-pathology assay, in stage II CC patients. IS emerged as the sole significant parameter for predicting disease-free survival (DFS) in high-risk patients. Moreover, IS effectively stratified patients who would benefit most from ACT based on their risk of recurrence, thus predicting their outcomes. Notably, our findings revealed that digital IS outperformed the visual quantitative assessment of the immune response conducted by expert pathologists. The latest edition of the WHO classification for digestive tumor has introduced the evaluation of the immune response, as assessed by IS, as desirable and essential diagnostic criterion. This supports the revision of current cancer guidelines and strongly recommends the implementation of IS into clinical practice as a patient stratification tool, to guide CC treatment decisions. This approach may provide appropriate personalized therapeutic decisions that could critically impact early-stage CC patient care.

Combination chemotherapy with trastuzumab in early-stage breast cancer: a meta-analysis and Bayesian decision analysis of different treatment regimens.

OBJECTIVE: HER2-positive breast cancer is a high-risk malignant tumor, and trastuzumab is an effective targeted therapy drug, but its optimal duration remains uncertain. To compare the efficacy and cost-effectiveness of different durations (6 months, 9 months, 12 months, and 18 months) of trastuzumab combined with chemotherapy in patients with early breast cancer by meta-analysis and Bayesian decision analysis. PATIENTS AND METHODS: Randomized controlled trials comparing the effectiveness of different durations of trastuzumab combination chemotherapy in early-stage breast cancer patients were collected by searching multiple databases. Data synthesis was performed using the R software, and a decision tree model was constructed to simulate the expected outcomes and anticipated costs associated with different treatment durations. RESULTS: This study included 9 randomized controlled trials involving 11,328 early-stage breast cancer patients. The meta-analysis results demonstrated that, compared to the control group, trastuzumab combination chemotherapy at different durations significantly improved disease-free survival and overall survival in early-stage breast cancer patients. Among the various treatment durations, it was observed that 12 months of trastuzumab combination chemotherapy, in comparison to other durations, significantly reduced the risk of recurrence and mortality in early-stage breast cancer patients while maintaining a favorable cost-effectiveness ratio. Bayesian decision analysis also confirmed that 12 months of trastuzumab combination chemotherapy is the optimal treatment duration. CONCLUSIONS: It is recommended to use 12 months of trastuzumab combination chemotherapy as the standard treatment for early-stage breast cancer patients.

Pilot study: a detailed analysis of the timing of immuno-inflammatory indices in gastric cancer, and their assessment together with TNM as supplementary prognostic factors.

An analysis of the prognostic impact of up to 36 immuno-inflammatory indices at 3 different times during the diagnostic-therapeutic process for gastric cancer. The dependent variable was disease-free survival at 3 years. The independent factors obtained were combined with TNM to provide an improved prognostic model.

Analysis of data from the PALOMA-3 trial confirms the efficacy of palbociclib and offers alternatives for novel assessment of clinical trials.

PURPOSE: There remains a need for novel therapies for patients with metastatic breast cancer (MBC). We explore the use of a novel biomarker of survival that could potentially expedite the testing of novel therapies. METHODS: We applied a tumor regression-growth model to radiographic measurement data from 393 women with MBC enrolled in PALOMA-3 examining efficacy of palbociclib in disease that had progressed on previous endocrine therapy. 261 and 132 women were randomized to fulvestrant plus palbociclib or placebo, respectively. We estimated rates of regression (d) and growth (g) of the sensitive and resistant fractions of tumors, respectively. We compared the median g of both arms. We examined the relationship between g and progression-free and overall survival (OS). RESULTS: As in other tumors, g is a biomarker of OS. In PALOMA-3, we found significant differences in g among patients with tumors sensitive to endocrine therapy but not amongst resistant tumors, emulating clinical trial results. Subgroup analysis found favorable g values in visceral metastases treated with palbociclib. Palbociclib efficacy demonstrated by slower g values was evident early in the trial, twelve weeks after the first 28 patients had been enrolled. CONCLUSION: Values of g, estimated using data collected while a patient is enrolled in a clinical trial is an excellent biomarker of OS. Our results correlate with the survival outcomes of PALOMA-3 and argue strongly for using g as a clinical trial endpoint to help inform go/no-go decisions, improve trial efficiency, and deliver novel therapies to patients sooner.

Progression-free survival assessment by local investigators versus blinded independent central review in randomized clinical trials in metastatic breast cancer: A systematic review and meta-analysis.

INTRODUCTION: In randomized clinical trials (RCTs), blinded independent central review (BICR) is used to minimize heterogeneity and bias associated with radiological response evaluation by local investigators. However, BICR adds costs and complexity to the trial management. We assessed the discrepancy index between progression-free survival (PFS) assessment by local investigators and by BICR in RCTs conducted in patients with metastatic breast cancer (MBC). METHODS: A systematic search of PubMed, Embase, Cochrane databases and conference proceedings (ASCO, SABCS, ESMO) was performed up to January 4, 2023 (PROSPERO: CRD42021229865). All RCTs published from 2000 to 2022, including MBC patients treated in first- or second-line, and reporting PFS assessed by local investigators and BICR were included. A discrepancy index between BICR-assessed and investigator-assessed HR was calculated for each trial and an overall combined DI was obtained using a fixed-effects model. The agreement between hazard ratios (HR) of PFS assessed by local investigators and BICR was measured using intraclass correlation coefficient (ICC). RESULTS: We analyzed 24 studies including 13,168 patients. Among them, 19 (79%) were in first-line, 18 (75%) were phase III trials and 23 (96%) had PFS as primary endpoint. The overall combined discrepancy index was 0.97 (95%CI 0.85-1.10; ICC 0.831, p < 0.001) suggesting no statistically significant difference in PFS assessment between local investigators and BICR. This result was consistent across all analyzed subgroups. CONCLUSIONS: The good concordance between local investigator and BICR assessments supports the reliability of local investigator-assessed PFS as primary endpoint for RCTs in MBC and questions the practical utility of implementing BICR in all RCTs.

Landmark Series: The Cancer Genome Atlas and the Study of Breast Cancer Disparities.

Race-related variation in breast cancer incidence and mortality are well-documented in the United States. The effect of genetic ancestry on disparities in tumor genomics, risk factors, treatment, and outcomes of breast cancer is less understood. The Cancer Genome Atlas (TCGA) is a publicly available resource that has allowed for the recent emergence of genome analysis research seeking to characterize tumor DNA and protein expression by ancestry as well as the social construction of race and ethnicity. Results from TCGA based studies support previous clinical evidence that demonstrates that American women with African ancestry are more likely to be afflicted with breast cancers featuring aggressive biology and poorer outcomes compared with women with other backgrounds. Data from TCGA based studies suggest that Asian women have tumors with favorable immune microenvironments and may experience better disease-free survival compared with white Americans. TCGA contains limited data on Hispanic/Latinx patients due to small sample size. Overall, TCGA provides important opportunities to define the molecular, biologic, and germline genetic factors that contribute to breast cancer disparities.

Assessment of nuclear grade-based recurrence risk classification in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive high-risk early breast cancer.

BACKGROUND: Histological grade (HG) has been used in the MonrachE trial to select patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive high-risk early breast cancer (EBC). Although nuclear grade (NG) is widely used in Japan, it is still unclear whether replacing HG with NG can appropriately select high-risk patients. METHODS: We retrospectively reviewed 647 patients with HR-positive, HER2-negative, node-positive EBC and classified them into the following four groups: group 1: ≥ 4 positive axillary lymph nodes (pALNs) or 1-3 pALNs and either grade 3 of both grading systems or tumors ≥ 5 cm; group 2: 1-3 pALNs, grade < 3, tumor < 5 cm, and Ki-67 ≥ 20%; group 3: 1-3 pALNs, grade < 3, tumor < 5 cm, and Ki-67 < 20%; and group 4: group 2 or 3 by HG classification but group 1 by NG classification. We compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) among the four groups using the Kaplan-Meier method with the log-rank test. RESULTS: Group 1 had a significantly worse 5-year IDFS and DRFS than groups 2 and 3 (IDFS 80.8% vs. 89.5%, P = 0.0319, 80.8% vs. 95.5%, P = 0.002; DRFS 85.2% vs. 95.3%, P = 0.0025, 85.2% vs. 98.4%, P < 0.001, respectively). Group 4 also had a significantly worse 5-year IDFS (78.0%) and DRFS (83.6%) than groups 2 and 3. CONCLUSIONS: NG was useful for stratifying the risk of recurrence in patients with HR-positive, HER2-negative, node-positive EBC and was the appropriate risk assessment for patient groups not considered high-risk by HG classification.

Evaluation of disease-free survival as a predictor of overall survival and assessment of real-world burden of disease recurrence in resected early-stage non-small cell lung cancer.

BACKGROUND: Intermediate endpoints, such as disease-free survival (DFS), have shown good correlation with overall survival (OS) in early-stage non-small cell lung cancer (NSCLC) clinical trials. However, real-world data are limited, and no previous real-world study has quantified the clinical and economic burden of disease recurrence. OBJECTIVE: To examine the association between real-world DFS (rwDFS) and OS and quantify the association between NSCLC recurrence and health care resource utilization (HCRU), health care costs, and OS in patients with resected early-stage NSCLC in the United States. METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare database (2007-2019) for patients with newly diagnosed stage IB (tumor size ≥ 4 cm) to IIIA (American Joint Committee on Cancer 7th edition) NSCLC who underwent surgery for primary NSCLC were analyzed in this retrospective observational study. Baseline patient demographic and clinical characteristics were described. rwDFS and OS were compared between patients with vs without recurrence using Kaplan-Meier curves and the log-rank test; their correlation was assessed using normal scores rank correlation. All-cause and NSCLC-related HCRU and health care costs were summarized, and mean monthly allcause and NSCLC-related health care costs were compared between cohorts using generalized linear models. RESULTS: Of the 1,761 patients who underwent surgery, 1,182 (67.1%) had disease recurrence; these patients had shorter OS from the index date and shorter subsequent OS at each postsurgery landmark (ie, 1, 3, and 5 years) than those without recurrence (all P < 0.001). OS and rwDFS were significantly correlated (0.57; P < 0.001). Patients with recurrence also had significantly higher all-cause and NSCLC-related HCRU and mean monthly all-cause and NSCLC-related health care costs during the study period. CONCLUSIONS: Postsurgery rwDFS was significantly correlated with OS in patients with early-stage NSCLC. Patients with postsurgery recurrence had a higher risk of death and incurred higher HCRU and health care costs than those without recurrence. These findings highlight the importance of preventing or delaying recurrence in patients with resected NSCLC. DISCLOSURES: Dr West is Senior Medical Director at AccessHope and an Associate Professor at City of Hope. He also serves on the advisory board for Amgen, AstraZeneca, Genentech/Roche, Gilead, Merck, Mirati Therapeutics, Regeneron, Summit Therapeutics, and Takeda and as a speaker for AstraZeneca and Merck. Drs Hu, Chirovsky, and Samkari are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and own stock/stock options in Merck & Co., Inc., Rahway, NJ, USA. Drs Zhang, Song, Gao, and Signorovitch, Mr Lerner, and Ms Jiang are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, which funded the development and conduct of this study and article. This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The collection of cancer incidence data used in this study was supported by the California Department of Public Health pursuant to California Health and Safety Code Section 103885; Centers for Disease Control and Prevention's National Program of Cancer Registries, under cooperative agreement 5NU58DP006344; the National Cancer Institute's SEER Program under contract HHSN261201800032I awarded to the University of California, San Francisco, contract HHSN261201800015I awarded to the University of Southern California, and contract HHSN261201800009I awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the authors and do not necessarily reflect the opinions of the State of California, Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their contractors and subcontractors.

A contemporary assessment of total neoadjuvant therapy (TNT) protocols for locally advanced rectal cancer: adoption and expert perspectives at German Cancer Society (DKG)-certified colorectal cancer centers.

PURPOSE: The treatment paradigm for locally advanced rectal cancer (LARC) is shifting toward the total neoadjuvant therapy (TNT) concept, which administered systemic chemotherapy in the neoadjuvant setting, either before or after chemoradiotherapy (CRT) or short-course radiotherapy (SCRT). First results have shown higher pathologic complete response (pCR) rates and a favorable impact on disease-free survival (DFS). Our study aimed to evaluate the current clinical practice and expert opinion regarding TNT for locally advanced rectal cancer across DKG (German Cancer Society)-certified colorectal cancer centers. METHODS: A comprehensive online questionnaire, constituted of 14 TNT-focused queries targeting patients with locally advanced rectal cancer, was conducted among DKG-certified colorectal cancer centers registered within the database of the Addz (Arbeitsgemeinschaft Deutscher Darmzentren) between December 2022 and January 2023. RESULTS: A significant majority (68%) indicated that they treated between 0 and 10 patients using a TNT protocol. Only a third (36%) of these centers participated in patient enrollment for a TNT study. Despite this, 84% of centers reported treating patients in a manner analogous to a TNT study, with the RAPIDO regimen being the most prevalent approach, employed by 60% of the respondents. The decision to adopt a TNT approach was primarily influenced by factors, such as the lower third of the rectum (93% of centers), cT4 stage (86% of centers), and a positive circumferential resection margin (80% of centers). Regarding concerns, 65% of the survey respondents expressed no reservations about the TNT concept, while 35% had concerns. In particular, there appears to be disagreement and uncertainty in regard to a clinical complete response and the "Watch and Wait" approach. While some centers adopt the watch-and-wait approach (42%), others only utilize it when extirpation is otherwise necessary (39%), and a portion still proceeds with surgery as initially planned (19%). The survey also addressed unmet needs, which were elaborated in the free-text responses. Overall, there was high interest in participating in planned observational studies. CONCLUSIONS: This study presents an overview of current clinical practice and unmet needs within DKG-certified German colorectal cancer centers. It is noteworthy that total neoadjuvant therapy (TNT) is predominantly performed outside of clinical trials. Moreover, across the centers, there is significant heterogeneity in handling clinical complete response and adopting the "watch and wait" approach. Further research is needed to establish standardization in the care of locally advanced rectal cancer.

Early assessment of circulating exosomal lncRNA-GC1 for monitoring neoadjuvant chemotherapy response in gastric cancer.

BACKGROUND: The timing of surgery for patients with gastric cancer (GC) who undergo neoadjuvant chemotherapy (neoCT) was mainly guided by serial radiologic imaging. However, an earlier assessment was indispensable to avoid delayed treatment for nonresponders and excessive toxicity for responders. Our previous study has identified circulating extracellular vesicles-derived lncRNA-GC1 as a biomarker for early detection and monitoring progression of GC. However, the potential role of neoCT remains poorly understood. METHODS: In this explorative biomarker analysis, we conducted a multi-cohort study to examine longitudinal levels of circulating extracellular vesicles-derived lncRNA-GC1 in 798 patients enrolled in the RESONANCE study (NCT01583361). Both circulating extracellular vesicles-derived lncRNA-GC1 and traditional gastrointestinal biomarkers were assessed at defined time nodes. Computed tomography (CT) scans were performed before treatment and 8-10 weeks and assessed based on the RECIST criteria. RESULTS: Circulating extracellular vesicles-derived lncRNA-GC1 could be detected in 96.3% of patients at baseline, and significant reductions were observed before cycle 2 (P<0.0001). Levels of circulating extracellular vesicles-derived lncRNA-GC1 showed a stronger correlation with tumor burden and exhibited earlier dynamic changes than the traditional gastrointestinal biomarkers during the first cycle of neoCT. Strong agreement was observed between circulating extracellular vesicles-derived lncRNA-GC1 response (reduction >50%) and radiographic response (Cohen's κ, 0.704). Importantly, circulating extracellular vesicles-derived lncRNA-GC1 maintained predictive value in two external cohorts. Patients with circulating extracellular vesicles-derived lncRNA-GC1 response showed superior disease-free survival [hazard ratio (HR), 0.6238; 95% CI, 0.4095-0.9501; P=0.0118] and overall survival (HR, 0.6131; 95% CI, 0.4016-0.9358; P=0.0090). CONCLUSION: Circulating extracellular vesicles-derived lncRNA-GC1 is an early marker of neoCT efficacy and predicts superior survival in GC patients treated with neoCT.

MRI Assessment of Extramural Venous Invasion Before and After Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer and Its Association with Disease-Free and Overall Survival.

BACKGROUND: Extramural venous invasion (EMVI) on baseline MRI is associated with poor prognosis in patients with locally advanced rectal cancer. This study investigated the association of persistent EMVI after total neoadjuvant therapy (TNT) (chemoradiotherapy and systemic chemotherapy) with survival. METHODS: Baseline MRI, post-TNT MRI, and surgical pathology data from 175 patients with locally advanced rectal cancer who underwent TNT and total mesorectal excision between 2010 and 2017 were retrospectively analyzed for evidence of EMVI. Two radiologists assessed EMVI status with disagreement adjudicated by a third. Pathologic EMVI status was assessed per departmental standards. Cox regression models evaluated the associations between EMVI and disease-free and overall survival. RESULTS: EMVI regression on both post-TNT MRI and surgical pathology was associated with disease-free survival (hazard ratio, 0.17; 95% confidence interval (CI), 0.04-0.64) and overall survival (hazard ratio, 0.11; 95% CI, 0.02-0.68). In an exploratory analysis of 35 patients with EMVI on baseline MRI, only six had EMVI on pathology compared with 18 on post-TNT MRI; these findings were not associated (p = 0.2). Longer disease-free survival was seen with regression on both modalities compared with remaining positive. Regression on pathology alone, independent of MRI EMVI status, was associated with similar improvements in survival. CONCLUSIONS: Baseline EMVI is associated with poor prognosis even after TNT. EMVI regression on surgical pathology is common even with persistent EMVI on post-TNT MRI. EMVI regression on surgical pathology is associated with improved DFS, while the utility of post-TNT MRI EMVI persistence for decision-making and prognosis remains unclear.

Disease-free survival as a predictor of overall survival in localized renal cell carcinoma following initial nephrectomy: A retrospective analysis of Surveillance, Epidemiology and End Results-Medicare datac.

OBJECTIVES: This study aimed to assess whether disease-free survival (DFS) may serve as a predictor for long-term survival among patients with intermediate-high risk or high risk renal cell carcinoma (RCC) post-nephrectomy when overall survival (OS) is unavailable. METHODS: The Surveillance, Epidemiology and End Results-Medicare database (2007-2016) was used to identify patients with non-metastatic intermediate-high risk and high risk RCC post-nephrectomy. Landmark analysis and Kendall's τ were used to evaluate the correlation between DFS and OS. Multivariable regression models were used to quantify the incremental OS post-nephrectomy associated with increased time to recurrence among patients with recurrence, adjusting for baseline covariates. RESULTS: A total of 643 patients were analyzed; mean age of 75 years; >95% of patients had intermediate-high risk RCC at diagnosis; 269 patients had recurrence post-nephrectomy. For patients with versus without recurrence at the landmark points of 1, 3, and 5 years post-nephrectomy, the 5-year OS were 37.0% versus 70.1%, 42.3% versus 72.8%, and 53.2% versus 78.6%, respectively. The Kendall's τ between DFS and OS post-nephrectomy was 0.70 (95% CI: 0.65, 0.74; p < 0.001). After adjusting for baseline covariates, patients with one additional year of time to recurrence were associated with 0.73 years longer OS post-nephrectomy (95% CI: 0.40, 1.05; p < 0.001). CONCLUSION: The significant positive association of DFS and OS among patients with intermediate-high risk and high risk RCC post-nephrectomy from this study supports the use of DFS as a potential predictor of OS for these patients when OS data are immature.

An objective assessment in newly diagnosed multiple myeloma to avoid treatment complications and strengthen therapy adherence.

In heterogeneous multiple myeloma (MM) patients treatment decisions are challenging. The hypothesis was that adaptation of treatment intensity (dose reduction [DR] vs. none) according to an objective risk score (revised-myeloma comorbidity index [R-MCI]) rather than physician judgement alone may improve therapy efficacy and avoid toxicities. We performed this study in 250 consecutive MM patients who underwent a prospective fitness assessment at our center, after having received induction protocols based on physicians' judgement. DR, serious adverse events (SAE), response, progression-free survival (PFS) and overall survival (OS) were compared in fitness (fit, intermediate-fit, frail), age (<60, ≥70 years [y]) and therapy intensity subgroups at baseline and follow-up. Fit and <60 y patients were mostly treated with full intensity, whereas frail and ≥70 y patients usually received DR. Hematological and non-hematological SAE were more frequently seen in frail versus ≥70 y patients. Dose adaptations were mainly necessary in frail patients. OS and PFS were similar in fit and intermediate-fit but significantly worse in frail patients (P=0.0245/P<0.0001), whereas in age-based subgroups, OS and PFS differences did not reach significance (P=0.1362/P=0.0569). Non-hematological SAE were another negative predictor for impaired OS and PFS (P=0.0054/P=0.0021). In the follow-up performed at a median of 11 months after the first fitness assessment, the R-MCI improved or remained stable in 90% versus deteriorated in only 10% of patients. In conclusion, separation by R-MCI/frailty-defined subgroups was superior to age-based subgroups and can be used to improve tailored treatment. Fitter patients benefit from intensive therapies, whereas frail patients bear a need for initial DR.

Preoperative computed tomography assessment of circumferential resection margin in retroperitonealized colon cancer predicts disease-free survival.

OBJECTIVES: The aim of this retrospective study was to predict circumferential resection margin (CRM) involvement on preoperative CT, and prognostic impact of CRM assessment by CT (ctCRM) in patients with retroperitonealized colon cancer. METHODS: This study included patients who underwent resection for ascending or descending colon cancer between July 2010 and February 2013. Positive ctCRM was defined as tumor distance to the retromesenteric plane of ≤ 1 mm. The origin of positive CRM was divided into primary tumor or other tumor components including lymph nodes, tumor deposits, or extramural venous invasions. Logistic regression analysis was performed to identify preoperative factors to predict pathologic CRM (pCRM). A Cox proportional hazards model was used in multivariable analysis to determine the preoperative factors affecting disease-free survival (DFS). RESULTS: A total of 274 patients (mean age, 64.0 years ± 11.0 [standard deviation]; 157 men) with retroperitonealized colon cancer were evaluated. Of 274 patients, 67 patients (24.5%) had positive CRM on surgical pathology. The accuracy of preoperative CT in predicting pCRM was 79.6% (218/274). Among preoperative factors, only CRM assessment on CT was independently associated with pCRM (p < 0.001). Positive ctCRM by primary tumor was an independent factor for DFS (HR, 3.362 [1.714-6.593]) and systemic recurrence (HR, 3.715 [1.787-7.724], but not for local recurrence on multivariable analyses. CONCLUSIONS: Preoperative CT can accurately predict pCRM, and positive ctCRM by primary tumor is an independent risk factor for DFS and systemic recurrence, but not for local recurrence in retroperitonealized colon cancer. KEY POINTS: • Preoperative CT can predict pathologic circumferential resection margin (CRM) with approximately 80% of accuracy in patients with retroperitonealized colon cancer. • Positive CRM by a primary tumor on preoperative CT is a poor prognostic factor for disease-free survival and systemic recurrence in patients with retroperitonealized colon cancer. • CRM involvement on CT was not associated with local recurrence in patients with retroperitonealized colon cancer.

Time interval between diagnosis to treatment of breast cancer and the impact of health insurance coverage: a sub analysis of the AMAZONA III Study (GBECAM 0115).

PURPOSE: Breast cancer (BC) is the most common type of cancer among women in Brazil. Evidence shows that delayed treatment onset is associated with increased mortality. This study aimed to evaluate median days between diagnosis and treatment and factors associated with delayed start of treatment (> 60 days after diagnosis): stage, treatment received, subtype, epidemiological characteristics, and type of healthcare coverage. METHODS: This analysis included 1709 stage I-III BC patients from AMAZONA III, a prospective, observational study, diagnosed from January 2016 to March 2018 in 22 centers in Brazil. RESULTS: The median number of days from diagnosis to beginning of first oncologic treatment was 46 days (IQR 28-75) overall, 43 days (IQR 25-75) for stage I disease, 49 days (IQR 28-81) for stage II, and 44 days (IQR 30-68) for stage III, (p = 0.1180). According to first treatment received, diagnosis-to-treatment interval was 43 days (IQR 29-65) for neoadjuvant chemotherapy and 48 days (IQR 26-81) for surgery. Diagnosis-to-treatment interval was higher in women treated in the public system versus the private system (56 vs. 34 days, p < 0.0001). Patients in the public system had an increased odds of delayed treatment initiation (OR 4.74 95% CI 3.09-7.26, p < .0001). The longer interval from diagnosis to treatment in the public system was independent of clinical stage, type of treatment (systemic vs surgery first), subtype and region of the country. CONCLUSION: By characterizing the delays in care delivery, our study will aid stakeholders to better design interventions and allocate resource to improve timely treatment for breast cancer in Brazil. CLINICALTRIALS: gov Identifier: NCT02663973, registered on January, 26th, 2016.

Combined assessment of muscle quality and quantity predicts oncological outcome in patients with esophageal cancer.

BACKGROUND: Sarcopenia consists of two dysregulation patterns of body composition, myopenia and myosteatosis. The aim of this study is to compare the preoperative status of various body composition indexes including our newly developed modified intramuscular adipose tissue content (mIMAC) to investigate these clinical values in esophageal cancer patients. METHOD: We assessed preoperative psoas muscle mass index (PMI), IMAC, and mIMAC in 150 esophageal cancer patients. RESULTS: Preoperative high IMAC and low mIMAC status were significantly associated with older age. Preoperative decreased mIMAC was significantly associated with advanced T classification and the presence of distant metastasis and low preoperative mIMAC was an independent prognostic factor for poor overall survival and disease-free survival in esophageal cancer patients. Combined assessment of preoperative mIMAC with PMI could help stratify risk for oncological outcomes. Finally, preoperative PMI and mIMAC were positively correlated with various nutritional factors in esophageal cancer patients. CONCLUSION: Combined assessment between preoperative PMI and mIMAC could stratify risk for oncological outcomes, and preoperative mIMAC might be surrogate marker for aging and nutritional status in esophageal cancer patients.

Delayed TME Surgery in a Watch-and-Wait Strategy After Neoadjuvant Chemoradiotherapy for Rectal Cancer: An Analysis of Hospital Costs and Surgical and Oncological Outcomes.

BACKGROUND: A watch-and-wait strategy for patients with rectal cancer with a clinical complete response after neoadjuvant chemoradiotherapy is a valuable alternative for rectal resection. However, there are patients who will have residual tumor or regrowth during watch and wait. OBJECTIVE: The aim of this study was to investigate safety and costs for patients who underwent delayed surgery after neoadjuvant chemoradiotherapy. DESIGN: This is a retrospective cohort study with prospectively collected data. SETTINGS: The study was conducted at a large teaching hospital. PATIENTS: Between January 2015 and May 2020, 622 new rectal cancer patients were seen, of whom 200 received neoadjuvant chemoradiotherapy. Ninety-four patients were included, 65 of whom underwent immediate surgery and 29 of whom required delayed surgery after an initial watch-and-wait approach. MAIN OUTCOME MEASURES: Outcome measures included 30-day postoperative morbidity rate, hospital costs. 2-year overall and disease-free survival. RESULTS: There was no difference in length of stay (9 vs 8; p = 0.83), readmissions (27.6% vs 10.0%; p = 0.10), surgical re-interventions (15.0% vs 3.4%; p = 0.16), or stoma-free rate (52.6% vs 31.0%; p = 0.09) between immediate and delayed surgery groups. Hospital costs were similar in the delayed group (€11,913 vs €13,769; p = 0.89). Two-year overall survival (93% vs 100%; p = 0.23) and disease-free survival (78% vs 81%; p = 0.47) rates were comparable. LIMITATIONS: Limitations included small sample size, follow-up time and retrospective design. CONCLUSION: Delayed surgery for regrowth in a watch-and-wait program or for persistent residual disease after a repeated assessment is not associated with an increased risk of postoperative morbidity or a significant rise in costs compared to immediate total mesorectal excision. There also appears to be no evident compromise in oncological outcome. Repeated response assessment in patients with a near complete clinical response after neoadjuvant chemoradiotherapy is a useful approach to identify more patients who can benefit from a watch-and-wait strategy. See Video Abstract at http://links.lww.com/DCR/B836 . CIRUGA DE TME RETRASADA EN UNA ESTRATEGIA DE WATCH AND WAIT DESPUS DE LA QUIMIORRADIOTERAPIA NEOADYUVANTE PARA CNCER DE RECTO UN ANLISIS DE COSTOS HOSPITALARIOS, Y DE RESULTADOS QUIRRGICOS Y ONCOLGICOS: ANTECEDENTES: Una estrategia de Watch and Wait para pacientes con cáncer de recto con una respuesta clínica completa después de quimiorradioterapia neoadyuvante es una alternativa valiosa en vez de resección rectal. Sin embargo, hay pacientes que tendrán tumor residual o un recrecimiento durante el Watch and Wait .OBJETIVO: El objetivo fue investigar la seguridad y los costos para los pacientes que se sometieron a una cirugía diferida después de la quimiorradioterapia neoadyuvante.DISEÑO: Este es un estudio de cohorte retrospectivo con datos recolectados prospectivamente.AJUSTE: El estudio se llevó a cabo en un gran hospital universitario.PACIENTES: Entre enero de 2015 y mayo de 2020, se atendieron 622 nuevos pacientes con cáncer de recto, de los cuales 200 recibieron quimiorradioterapia neoadyuvante. Se incluyeron 94 pacientes, de los cuales 65 se sometieron a cirugía inmediata y 29 pacientes requirieron cirugía diferida después de un enfoque inicial de observación y espera.PRINCIPALES MEDIDAS DE RESULTADO: se incluyeron la tasa de morbilidad posoperatoria a 30 días, los costos hospitalarios y las sobrevidas general y libre de enfermedad a dos años.RESULTADOS: No hubo diferencia en la duración de la estancia (9 vs 8, p = 0,83), reingresos (27,6% vs 10,0%, p = 0,10), reintervenciones quirúrgicas (15,0% vs 3,4%, p = 0,16) y tasa libre de estoma (52,6% vs 31,0%, p = 0,09) entre los grupos de cirugía inmediata y tardía. Los costos hospitalarios fueron similares en el grupo retrasado (11913 € frente a 13769 €, p = 0,89). Las tasas de sobrevida general a dos años (93% frente a 100%, p = 0,23) y sobrevida libre de enfermedad (78% frente a 81%, p = 0,47) fueron comparables.LIMITACIONES: Tamaño de muestra pequeño, tiempo de seguimiento y diseño retrospectivo.CONCLUSIÓN: La cirugía tardía para el recrecimiento en un programa de Watch and Wait o para la enfermedad residual persistente después de una evaluación repetida no se asocia con un riesgo mayor de morbilidad posoperatoria ni con un aumento significativo en los costos, en comparación con la escisión total de mesorrecto inmediata. Tampoco parece haber un compromiso evidente en el resultado oncológico. La evaluación repetida de la respuesta en pacientes con una respuesta clínica casi completa después de la quimiorradioterapia neoadyuvante es un enfoque útil para identificar más pacientes que pueden beneficiarse de una estrategia de Watch and Wait . Consulte Video Resumen en http://links.lww.com/DCR/B836 . (Traducción-Dr. Juan Carlos Reyes ).

Surgical outcomes of T4b oral cancers: assessment of prognostic factors and a need to re-evaluate the current staging system.

T4b oral cancer is a broad umbrella term for all advanced oral cancers, the prognosis of which varies drastically for disease of the same stage, according to the extent of the masticator space involvement. This was a retrospective observational study including all consecutive T4b oral squamous cell carcinoma patients treated surgically between January 2015 and January 2016 and followed up until January 2020. The disease was classified as upper disease or lower disease based on the anatomical location in relation to an imaginary plane passing through the base of the retromolar trigone. The prime objective was to evaluate overall survival and prognostic factors affecting overall survival. The projected 5-year overall and disease-free survival rates were 40.7% and 35.6%, respectively. The assessment of prognostic factors revealed that lower disease (lower anatomical subsites), bone invasion, and lymph nodal spread significantly affected survival. Patients with disease in an upper anatomical location without bone and nodal involvement can achieve fairly good survival (projected 5-year overall survival of 64.2%) when compared to the other subsets of patients. We propose a re-evaluation of the current staging system based on the prognostic features, so that all patients are not considered under a single stage, since their survival differs significantly.