Use of deep learning to evaluate tumor microenvironmental features for prediction of colon cancer recurrence.

Deep learning may detect biologically important signals embedded in tumor morphologic features that confer distinct prognoses. Tumor morphological features were quantified to enhance patient risk stratification within DNA mismatch repair (MMR) groups using deep learning. Using a quantitative segmentation algorithm (QuantCRC) that identifies 15 distinct morphological features, we analyzed 402 resected stage III colon carcinomas (191 d-MMR; 189 p-MMR) from participants in a phase III trial of FOLFOX-based adjuvant chemotherapy. Results were validated in an independent cohort (176 d-MMR; 1094 p-MMR). Association of morphological features with clinicopathologic variables, MMR, KRAS, BRAFV600E, and time-to-recurrence (TTR) was determined. Multivariable Cox proportional hazard models were developed to predict TTR. Tumor morphological features differed significantly by MMR status. Cancers with p-MMR had more immature desmoplastic stroma. Tumors with d-MMR had increased inflammatory stroma, epithelial tumor-infiltrating lymphocytes (TILs), high grade histology, mucin, and signet ring cells. Stromal subtype did not differ by BRAFV600E or KRAS status. In p-MMR tumors, multivariable analysis identified tumor-stroma ratio (TSR) as the strongest feature associated with TTR [HRadj 2.02; 95% CI,1.14-3.57; P=0.018; 3-year recurrence: 40.2% vs 20.4%; Q1 vs Q2-4]. Among d-MMR tumors, extent of inflammatory stroma [continuous HRadj 0.98; 95% CI,0.96-0.99; P=0.028; 3-year recurrence: 13.3% vs 33.4%, Q4 vs Q1] and N stage were the most robust prognostically. Association of TSR with TTR was independently validated. In conclusion, QuantCRC can quantify morphological differences within MMR groups in routine tumor sections to determine their relative contributions to patient prognosis, and may elucidate relevant pathophysiologic mechanisms driving prognosis.

Integrating Patient-Reported Outcomes Into Prognostication in Gastroesophageal Cancer: Results of a Population-Based Retrospective Cohort Analysis.

BACKGROUND: Patient-reported outcomes measures (PROM) are self-reflections of an individual's physical functioning and emotional well-being. The Edmonton Symptom Assessment Scale (ESAS) is a simple and validated PRO tool of 10 common symptoms and a patient-reported functional status (PRFS) measure. The prognostic value of this tool is unknown in patients with gastroesophageal cancer (GEC). In this study, we examined the association between the ESAS score and overall survival (OS) in patients with GEC, the prognostication difference between ESAS and Eastern Cooperative Oncology Group (ECOG), and assessed the correlation between PRFS and the physician-reported ECOG performance status (PS). METHODS: The study was a retrospective cohort study of 211 patients with GEC with localized (stages I-III) and metastatic disease who completed at least one baseline ESAS prior to treatment. Patients were grouped into 3 cohorts based on ESAS score. OS was assessed using the Kaplan-Meier method, and the concordance index (c-index) was calculated for ESAS and physician-reported ECOG. The agreement between PRFS and physician-ECOG was also assessed. RESULTS: In total, 211 patients were included. The median age was 60.8 years; 90% of patients were ECOG PS 0-1; 38% of patients were stages I-III, while 62% were de novo metastatic patients. Median OS in low, moderate, high symptom burden (SB) patients' cohorts was 19.17 m, 16.39 mm, and 12.68 m, respectively (P < .04). The ability to predict death was similar between physician-ECOG and ESAS (c-index 0.56 and 0.5753, respectively) and PRFS and physician-ECOG (c-index of 0.5615 and 0.5545, respectively). The PS agreement between patients and physicians was 50% with a weighted Kappa of 0.27 (95% CI: 0.17-0.38). CONCLUSION: Patient's SB seems to carry a prognostic significance. ESAS and physician-reported ECOG exhibit comparable prognostic values. Physicians and patients can frequently have divergent opinions on PS. ESAS takes a patient-centered approach and should be encouraged in practice among patients with GEC as an additional tool for prognostication.

Improved Risk-Stratification Scheme for Mismatch-Repair Proficient Stage II Colorectal Cancers Using the Digital Pathology Biomarker QuantCRC.

PURPOSE: There is a need to improve current risk stratification of stage II colorectal cancer to better inform risk of recurrence and guide adjuvant chemotherapy. We sought to examine whether integration of QuantCRC, a digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines. EXPERIMENTAL DESIGN: ASCO and QuantCRC-integrated schemes were applied to a cohort of 398 mismatch-repair proficient (MMRP) stage II colorectal cancers from three large academic medical centers. The ASCO stage II scheme was taken from recent guidelines. The QuantCRC-integrated scheme utilized pT3 versus pT4 and a QuantCRC-derived risk classification. Evaluation of recurrence-free survival (RFS) according to these risk schemes was compared using the log-rank test and HR. RESULTS: Integration of QuantCRC provides improved risk stratification compared with the ASCO scheme for stage II MMRP colorectal cancers. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared with the ASCO scheme (62.5% vs. 42.2%) without compromising excellent 3-year RFS. The QuantCRC-integrated scheme provided larger HR for both intermediate-risk (2.27; 95% CI, 1.32-3.91; P = 0.003) and high-risk (3.27; 95% CI, 1.42-7.55; P = 0.006) groups compared with ASCO intermediate-risk (1.58; 95% CI, 0.87-2.87; P = 0.1) and high-risk (2.24; 95% CI, 1.09-4.62; P = 0.03) groups. The QuantCRC-integrated risk groups remained prognostic in the subgroup of patients that did not receive any adjuvant chemotherapy. CONCLUSIONS: Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance for stage II MMRP colorectal cancers.

New Sarculator Prognostic Nomograms for Patients With Primary Retroperitoneal Sarcoma: Case Volume Does Matter.

OBJECTIVE: To update the current Sarculator retroperitoneal sarcoma (RPS) prognostic nomograms considering the improvement in patient prognosis and the case volume effect. BACKGROUND: Survival of patients with primary RPS has been increasing over time, and the volume-outcome relationship has been well recognized. Nevertheless, the specific impact on prognostic nomograms is unknown. METHODS: All consecutive adult patients with primary localized RPS treated at 8 European and North American sarcoma reference centers between 2010 and 2017 were included. Patients were divided into 2 groups: high-volume centers (HVC, ≥13 cases/year) and low-volume centers (LVC, <13 cases/year). Primary end points were overall survival (OS) and disease-free survival (DFS). Multivariable analyses for OS and DFS were performed. The nomograms were updated by recalibration. Nomograms performance was assessed in terms of discrimination (Harrell C index) and calibration (calibration plot). RESULTS: The HVC and LVC groups comprised 857 and 244 patients, respectively. The median annual primary RPS case volume (interquartile range) was 24.0 in HVC (15.0-41.3) and 9.0 in LVC (1.8-10.3). Five-year OS was 71.4% (95% CI: 68.3%-74.7%) in the HVC cohort and 63.3% (56.8%-70.5%) in the LVC cohort ( P =0.012). Case volume was associated with both OS (LVC vs. HVC hazard ratio 1.40, 95% CI: 1.08-1.82, P =0.011) and DFS (hazard ratio 1.93, 95% CI: 1.57-2.37, P <0.001) at multivariable analyses. When applied to the study cohorts, the Sarculator nomograms showed good discrimination (Harrell C index between 0.68 and 0.73). The recalibrated nomograms showed good calibration in the HVC group, whereas the original nomograms showed good calibration in the LVC group. CONCLUSIONS: New nomograms for patients with primary RPS treated with surgery at high-volume versus low-volume sarcoma reference centers are available in the Sarculator app.

Tumor Budding Assessment in Colorectal Carcinoma: Normalization Revisited.

Tumor budding (TB) is a powerful prognostic factor in colorectal cancer (CRC). An internationally standardized method for its assessment (International Tumor Budding Consensus Conference [ITBCC] method) has been adopted by most CRC pathology protocols. This method requires that TB counts are reported by field area (0.785 mm 2 ) rather than objective lens and a normalization factor is applied for this purpose. However, the validity of this approach is yet to be tested. We sought to validate the ITBCC method with a particular emphasis on normalization as a tool for standardization. In a cohort of 365 stage I-III CRC, both normalized and non-normalized TB were significantly associated with disease-specific survival and recurrence-free survival ( P <0.0001). Examining both 0.95 and 0.785 mm 2 field areas in a subset of patients (n=200), we found that normalization markedly overcorrects TB counts: Counts obtained in a 0.95 mm 2 hotspot field were reduced by an average of 17.5% following normalization compared with only 3.8% when counts were performed in an actual 0.785 mm 2 field. This resulted in 45 (11.3%) cases being downgraded using ITBCC grading criteria following normalization, compared with only 5 cases (1.3%, P =0.0007) downgraded when a true 0.785 mm 2 field was examined. In summary, the prognostic value of TB was retained regardless of whether TB counts in a 0.95 mm 2 field were normalized. Normalization resulted in overcorrecting TB counts with consequent downgrading of most borderline cases. This has implications for risk stratification and adjuvant treatment decisions, and suggests the need to re-evaluate the role of normalization in TB assessment.

Clinico-demographic characteristics and outcomes of radiation-induced sarcomas (RIS): a CanSaRCC study.

Background: Radiation-induced sarcomas (RIS) tend to have aggressive behaviour and because of their rarity, the most appropriate management for these malignancies is uncertain. Objectives: Using the Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) database, a national sarcoma registry, we aimed to investigate prognostic factors and outcomes for RIS. Design: Retrospective study of RIS patients treated from 1996 to 2021 at three Canadian centres. Methods: RIS was defined as a sarcoma arising in a previously irradiated field following a 3+ year latency period, whose histology was distinct from the initially irradiated tumour. Clinicopathologic and treatment-related information was extracted from the CanSaRCC database. Overall survival (OS) was defined as the time from RIS diagnosis to death from any cause. Response rate (RR) to neoadjuvant chemotherapy (NACT) was based on physician assessment. Time-to-event analyses were estimated using the Kaplan-Meier method, with Cox regression for multivariate analysis. We considered a two-tailed p-value of <0.05 as statistically significant. Results: One hundred seven tumours met the criteria for RIS and were divided into three subgroups: breast angiosarcoma (BAS, n = 54), osteosarcoma (OST, n = 16), and other soft-tissue sarcomas (STS, n = 37). Patients were mostly female (n = 85, 79%), treated initially for breast carcinomas (n = 54, 50.5%), and diagnosed with high-grade tumours (n = 61/71, 86%). None had evidence of synchronous metastasis. Patients with OST were younger (median age: 48 years, p < 0.001), and BAS had the shortest latency interval (8 versus 18 years for OST/STS, p < 0.001). Most patients underwent surgery, 76% (n = 76/100) R0; 24% (n = 26) received radiation therapy, mostly (n = 15, 57.7%) neoadjuvant. Among those receiving chemotherapy, 30 (75%) underwent NACT; among patients with documented response assessment, the RR was 68% (n = 17/25), being even higher in the BAS population (89.5%, n = 13/17). Median OS was 53 months (95% CI 34-101), with a 5-year OS of 47.6%; larger tumour size, high histologic grade and older age were independent prognostic factors for worse OS. Conclusion: Surgery is standard, and NACT might be useful to downsize large lesions, especially in BAS patients. Raising RIS awareness is fundamental to promoting appropriate management and fostering research through multi-institutional collaborations.

Combination of clinical, radiomic, and "delta" radiomic features in survival prediction of metastatic gastroesophageal adenocarcinoma.

Objectives: To identify combined clinical, radiomic, and delta-radiomic features in metastatic gastroesophageal adenocarcinomas (GEAs) that may predict survival outcomes. Methods: A total of 166 patients with metastatic GEAs on palliative chemotherapy with baseline and treatment/follow-up (8-12 weeks) contrast-enhanced CT were retrospectively identified. Demographic and clinical data were collected. Three-dimensional whole-lesional radiomic analysis was performed on the treatment/follow-up scans. "Delta" radiomic features were calculated based on the change in radiomic parameters compared to the baseline. The univariable analysis (UVA) Cox proportional hazards model was used to select clinical variables predictive of overall survival (OS) and progression-free survival (PFS) (p-value <0.05). The radiomic and "delta" features were then assessed in a multivariable analysis (MVA) Cox model in combination with clinical features identified on UVA. Features with a p-value <0.01 in the MVA models were selected to assess their pairwise correlation. Only non-highly correlated features (Pearson's correlation coefficient <0.7) were included in the final model. Leave-one-out cross-validation method was used, and the 1-year area under the receiver operating characteristic curve (AUC) was calculated for PFS and OS. Results: Of the 166 patients (median age of 59.8 years), 114 (69%) were male, 139 (84%) were non-Asian, and 147 (89%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. The median PFS and OS on treatment were 3.6 months (95% CI 2.86, 4.63) and 9 months (95% CI 7.49, 11.04), respectively. On UVA, the number of chemotherapy cycles and number of lesions at the end of treatment were associated with both PFS and OS (p < 0.001). ECOG status was associated with OS (p = 0.0063), but not PFS (p = 0.054). Of the delta-radiomic features, delta conventional HUmin, delta gray-level zone length matrix (GLZLM) GLNU, and delta GLZLM LGZE were incorporated into the model for PFS, and delta shape compacity was incorporated in the model for OS. Of the treatment/follow-up radiomic features, shape compacity and neighborhood gray-level dependence matrix (NGLDM) contrast were used in both models. The combined 1-year AUC (Kaplan-Meier estimator) was 0.82 and 0.81 for PFS and OS, respectively. Conclusions: A combination of clinical, radiomics, and delta-radiomic features may predict PFS and OS in GEAs with reasonable accuracy.

Desmoid Tumors in Familial Adenomatous Polyposis Patients: Favorable Outcomes with Multidisciplinary Management.

OBJECTIVE: In this study, we aimed to describe the clinical features, management, and outcomes of desmoid tumors (DTs) in familial adenomatous polyposis (FAP) patients at a high-volume sarcoma center. METHODS: Consecutive patients with FAP and DTs were identified from our institutional databases (1985-2021). Patient demographics, treatment, and outcomes were described. Categorical data were compared using Fisher's exact test, and Kaplan-Meier curves were used to estimate progression-free survival (PFS). RESULTS: Forty-five patients with 67 DTs were identified: 39 mesenteric or retroperitoneal (58.2%), 17 abdominal wall (25.4%), 4 extremity (6%), 4 breast (6%) and 3 back (4.4%). Severe DT symptoms were present in 12 patients (26.7%). Initial treatments per tumor were observation in 30 (44.8%) DTs, chemotherapy in 15 (22.4%) DTs, surgery in 10 (14.9%) DTs, and other systemic therapies in 10 (14.9%) DTs. The majority of DTs remained stable with observation or a single intervention (77.8%). Median PFS was 23.4 years (95% confidence interval 7.6-39.2). In the 12 severely symptomatic patients, four patients required more than two interventions for DT control. At a median follow-up of 6.0 years (range 0.7-35.8 years), 33 (73.3%) patients were alive with disease, 7 (15.6%) were alive without disease, and 5 (11.1%) died of other causes. No patients died of DT-related complications. CONCLUSIONS: The majority of DTs in FAP patients remained stable with observation or a single intervention. There were no DT-related deaths; however, 12 of 45 patients (26.7%) experienced significant tumor morbidity and required more interventions for disease control. Further studies on quality of life are required.

Outcome After Surgical Treatment of Dermatofibrosarcoma Protuberans (DFSP): Does it Require Extensive Follow-up and What is an Adequate Resection Margin?

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumour of indeterminate malignant potential. The mainstay treatment for DFSP is surgical resection. Given the reported high local recurrence rate, the ideal resection margin for DFSP is unclear. The purpose of this study was to ascertain the local recurrence and metastatic rate of DFSP and DFSP with fibrosarcomatous degeneration (FS-DFSP), with specific attention to margin status in an attempt to address the issue of margin adequacy. METHODS: Patients treated for DFSP at a single sarcoma centre were identified from a prospective database. DFSP and FS-DFSP patients with and without prior surgery were included. Patients were followed after surgery to monitor complications, local recurrence and metastasis. RESULTS: The study included 200 patients: 166 patients with DFSP and 34 patients with FS-DFSP. In the DFSP group, nine patients (5.4%) had positive margins, one case (0.6%) developed local recurrence (LR) and no patients developed distant metastases. In the FS-DFSP group, seven patients (20.6%) had positive margins, six patients (17.6%) developed local recurrence (LR) and eight patients (23.5%) developed distant metastases, of which three (37.5%) were in the lungs, one (12.5%) in bone and four (50%) in other soft tissue sites. DISCUSSION AND CONCLUSION: Local recurrence and metastases are extremely rare in patients with DFSP. Achieving a negative as opposed to a wide surgical margin may be sufficient to avoid local recurrence of most DFSP. We suggest that no ongoing surveillance for local or systemic relapse is required for DFSP patients after negative margin resection. For FS-DFSP, we recommend the same surveillance schedule, based on tumour grade, as other soft tissue sarcoma.

Comparison of Four Clinical Prognostic Scores in Patients with Advanced Gastric and Esophageal Cancer.

BACKGROUND: Prognostic scores that can identify patients at risk for early death are needed to aid treatment decision-making and patient selection for clinical trials. We compared the accuracy of four scores to predict early death (within 90 days) and overall survival (OS) in patients with metastatic gastric and esophageal (GE) cancer. METHODS: Advanced GE cancer patients receiving first-line systemic therapy were included. Prognostic risks were calculated using: Royal Marsden Hospital (RMH), MD Anderson Cancer Centre (MDACC), Gustave Roussy Immune (GRIm-Score), and MD Anderson Immune Checkpoint Inhibitor (MDA-ICI) scores. Overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to analyze associations between prognostic scores and OS. The predictive discrimination was estimated using Harrell's c-index. Predictive ability for early death was measured using time-dependent AUCs. RESULTS: In total, 451 patients with metastatic GE cancer were included. High risk patients had shorter OS for all scores (RMH high- vs. low-risk median OS 7.9 vs. 12.2 months, P < .001; MDACC 6.8 vs. 11.9 months P < .001; GRIm-Score 5.3 vs. 13 months, P < .001; MDA-ICI 8.2 vs. 12.2 months, P < .001). On multivariable analysis, each prognostic score was significantly associated with OS. The GRIm-Score had the highest predictive discrimination and predictive ability for early death. CONCLUSIONS: The GRIm-Score had the highest accuracy in predicting early death and OS. Clinicians may use this score to identify patients at higher risk of early death to guide treatment decisions including clinical trial enrolment. This score could also be used as a stratification factor in future clinical trial designs.

Prognostic Significance of Tumour Budding and Desmoplastic Reaction in Intestinal-Type Gastric Adenocarcinoma.

Objective. Tumour budding and desmoplastic reactions in peritumoural stroma are features of the tumour microenvironment that are associated with colorectal cancer prognosis but have not been as thoroughly examined in gastric cancer. We aimed to further characterize the prognostic role of tumour budding and desmoplastic reaction in gastric adenocarcinoma with intestinal differentiation. Methods. 76 curative gastrectomy specimens were identified, excluding post-neoadjuvant cases or cases with >50% diffuse-type histology. Tumour budding was defined and graded according to the International Tumor Budding Consensus Conference recommendations and desmoplastic reaction was classified as described by Ueno et al 2017. Tumour budding and desmoplastic reaction were analyzed for associations with pathologic features and clinical outcomes. Results. Tumour budding was associated with pT (P < .001), pN (P < .004), overall stage (P < .001), LVI (P < .001) and PNI (P = .002). Desmoplastic reaction was associated with pT (P < .001), pN (P = .005), overall stage (P = .031) and PNI (P < .001), but not LVI. Survival analysis showed decreased overall survival (OS) and recurrence-free survival (RFS) for intermediate and high grade tumour budding (P = .031, .014 respectively). Immature stroma was significantly associated with RFS but not OS. Neither tumour budding nor desmoplastic reaction were independent predictors of OS or RFS on multivariate analysis in this cohort. Conclusion. Tumour budding and desmoplastic reaction were associated with known pathologic risk factors. Prognostically, tumour budding was associated with OS and RFS while desmoplastic reaction was associated with RFS only. Our data suggest that tumour budding and desmoplastic reaction have prognostic value in intestinal-type gastric adenocarcinoma.

Retrospective Analysis of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study by the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas. BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series. METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management. RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of patients being female. Symptomatic presentation comprised 40.9% of cases, and tumors were often located in the extra-adrenal retroperitoneum (67.1%). At baseline, the median maximum tumor diameter was 7.2 cm. One hundred sixteen (35.4%) patients underwent active surveillance, whereas 212 (64.6%) patients underwent resection with 74.5% of operative cases achieving an R0/R1 resection. Serial tumor evaluations showed that malignant transformation to neuroblastoma was rare (0.9%, N=3). Tumors undergoing surveillance had a median follow-up of 1.9 years, with 92.2% of ganglioneuromas stable in size. With a median follow-up of 3.0 years for resected tumors, 84.4% of patients were disease free after resections, whereas recurrences were observed in 4 (1.9%) patients. CONCLUSIONS: Most ganglioneuromas have indolent disease courses and rarely transform to neuroblastoma. Thus, active surveillance may be appropriate for benign and asymptomatic tumors particularly when the risks of surgery outweigh the benefits. For symptomatic or growing tumors, resection may be curative.

Preoperative Radiotherapy in Patients With Primary Retroperitoneal Sarcoma: EORTC-62092 Trial (STRASS) Versus Off-trial (STREXIT) Results.

OBJECTIVE: The aim of the present study was to compare the effect of radiotherapy (RT) on abdominal recurrence-free survival (ARFS) in patients with primary retroperitoneal sarcoma treated in the EORTC-STBSG-62092 (STRASS) phase 3 randomized controlled trial (STRASS cohort) and off-trial (STREXIT cohort) and to pool STRASS and STREXIT data to test the hypothesis that RT improves ARFS in patients with liposarcoma. BACKGROUND: The STRASS trial did not show any difference in ARFS between patients treated with preoperative radiotherapy+surgery (RT+S) versus surgery alone (S). METHODS: All consecutive adult patients not enrolled in STRASS and underwent curative-intent surgery for a primary retroperitoneal sarcoma with or without preoperative RT between 2012 and 2017 (STRASS recruiting period) among ten STRASS-recruiting centres formed the STREXIT cohort. The effect of RT in STREXIT was explored with a propensity score (PS)-matching analysis. Primary endpoint was ARFS defined as macroscopically incomplete resection or abdominal recurrence or death of any cause, whichever occurred first. RESULTS: STRASS included 266 patients, STREXIT included 831 patients (727 after excluding patients who received preoperative chemotherapy, 202 after 1:1 PS-matching). The effect of RT on ARFS in STRASS and 1:1 PS-matched STREXIT cohorts, overall and in patients with liposarcoma, was similar. In the pooled cohort analysis, RT administration was associated with better ARFS in patients with liposarcoma [N=321, hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.42-0.89]. In particular, patients with well-differentiated liposarcoma and G1-2 dedifferentiated liposarcoma (G1-2 DDLPS, n=266) treated with RT+S had better ARFS (HR, 0.63; 95% CI, 0.40-0.97) while patients with G3 DDLPS and leiomyosarcoma had not. At the current follow-up, there was no association between RT and overall survival or distant metastases-free survival. CONCLUSIONS: In this study, preoperative RT was associated with better ARFS in patients with primary well-differentiated liposarcoma and G1-2 DDLPS.

How to treat liposarcomas located in retroperitoneum.

Almost half of retroperitoneal (RP) sarcomas are liposarcomas (LPS). The large majority of RP LPS are either well-differentiated LPS (WDLPS) or dedifferentiated LPS (DDLPS), these latter further classified according to grading in G2 and G3 DDLPS. Surgery is the only potentially curative treatment to achieve local control and possibly cure in primary localized disease. Over the last decade, a better delineation of the different histology-specific patterns of failure and the development of nomograms predictors of outcome has led to a better management of these rare tumors, with a special focus on non-surgical treatments. Available evidences - although far from exhaustive - show that radiation therapy might have a role, if any, as neoadjuvant treatment in locally aggressive histologies (i.e. WDLPS and G2 DDLPS), while it does not seem beneficial for histologies with a higher metastatic risk (i.e. G3 DDLPS and leiomyosarcoma). Neoadjuvant chemotherapy, instead, can be considered to reduce the risk of distant metastasis while waiting for the results of an ongoing RCT (STRASS-2) evaluating its effect in these tumors. However, given the rarity of these diseases and the subsequent lack of strong evidences to guide treatment, outcome improvement in these patients remains a challenge. Patients' referral to a sarcoma center where a dedicated specialized multidisciplinary team tailor optimal treatment on a case-by-case basis is crucial to ensure these patients the best outcome. Refining available nomograms - e.g including molecular variables - and identifying predictors of response/toxicity to chemotherapy and immunotherapy might be significantly helpful in tailoring treatments to the patient's characteristics. Also, new systemic agents are eagerly awaited for improving the management further.

Quantitative Pathologic Analysis of Digitized Images of Colorectal Carcinoma Improves Prediction of Recurrence-Free Survival.

BACKGROUND & AIMS: To examine whether quantitative pathologic analysis of digitized hematoxylin and eosin slides of colorectal carcinoma (CRC) correlates with clinicopathologic features, molecular alterations, and prognosis. METHODS: A quantitative segmentation algorithm (QuantCRC) was applied to 6468 digitized hematoxylin and eosin slides of CRCs. Fifteen parameters were recorded from each image and tested for associations with clinicopathologic features and molecular alterations. A prognostic model was developed to predict recurrence-free survival using data from the internal cohort (n = 1928) and validated on an internal test (n = 483) and external cohort (n = 938). RESULTS: There were significant differences in QuantCRC according to stage, histologic subtype, grade, venous/lymphatic/perineural invasion, tumor budding, CD8 immunohistochemistry, mismatch repair status, KRAS mutation, BRAF mutation, and CpG methylation. A prognostic model incorporating stage, mismatch repair, and QuantCRC resulted in a Harrell's concordance (c)-index of 0.714 (95% confidence interval [CI], 0.702-0.724) in the internal test and 0.744 (95% CI, 0.741-0.754) in the external cohort. Removing QuantCRC from the model reduced the c-index to 0.679 (95% CI, 0.673-0.694) in the external cohort. Prognostic risk groups were identified, which provided a hazard ratio of 2.24 (95% CI, 1.33-3.87, P = .004) for low vs high-risk stage III CRCs and 2.36 (95% CI, 1.07-5.20, P = .03) for low vs high-risk stage II CRCs, in the external cohort after adjusting for established risk factors. The predicted median 36-month recurrence rate for high-risk stage III CRCs was 32.7% vs 13.4% for low-risk stage III and 15.8% for high-risk stage II vs 5.4% for low-risk stage II CRCs. CONCLUSIONS: QuantCRC provides a powerful adjunct to routine pathologic reporting of CRC. A prognostic model using QuantCRC improves prediction of recurrence-free survival.

Investigating the mechanisms of peritoneal metastasis in gastric adenocarcinoma using a novel ex vivo peritoneal explant model.

Gastric adenocarcinoma, commonly known as stomach cancer, has a predilection for metastasis to the peritoneum, which portends limited survival. The peritoneal metastatic cascade remains poorly understood, and existing models fail to recapitulate key elements of the interaction between cancer cells and the peritoneal layer. To explore the underlying cellular and molecular mechanisms of peritoneal metastasis, we developed an ex vivo human peritoneal explant model. Fresh peritoneal tissue samples were suspended, mesothelial layer down but without direct contact, above a monolayer of red-fluorescent dye stained AGS human gastric adenocarcinoma cells for 24 h, then washed thoroughly. Implantation of AGS cells within the explanted peritoneum and invasion beyond the mesothelial layer were examined serially using real-time confocal fluorescence microscopy. Histoarchitecture of the explanted peritoneum was preserved over 5 days ex vivo. Both implantation and invasion were suppressed by restoration of functional E-cadherin through stable transfection of AGS cells, demonstrating sensitivity of the model to molecular manipulation. Thus, our ex vivo human peritoneal explant model permits meaningful investigation of the pathways and mechanism that contribute to peritoneal metastasis. The model will facilitate screening of new therapies that target peritoneal dissemination of gastric, ovarian and colorectal cancer.

Impact of the coronavirus disease 2019 pandemic on delivery of and models for supportive and palliative care for oncology patients.

PURPOSE OF REVIEW: Supportive and palliative care services have been an important component of the overall COVID-19 pandemic response. However, significant changes in the provision and models of care were needed in order to optimize the care delivered to vulnerable cancer patients. This review discusses the evolution of palliative and supportive care service in response to the pandemic, and highlights remaining challenges. RECENT FINDINGS: Direct competition for resources, as well as widespread implementation of safety measures resulted in major shifts in the mode of assessment and communication with cancer patients by supportive care teams. Telemedicine/virtual consultation and follow-up visits became an integral strategy, with high uptake and satisfaction amongst patients, families and providers. However, inequities in access to the required technologies were sometimes exposed. Hospice/palliative care unit (PCU) bed occupancy declined markedly because of restrictive visitation policies. Collection of patient-reported outcome (PRO) data was suspended in many cancer centers, with resulting under-recognition of anxiety and depression in ambulatory patients. As in many other areas, disparities in delivery of supportive and palliative care were magnified by the pandemic. SUMMARY: Virtual care platforms have been widely adopted and will continue to be used to include a wider circle of family/friends and care providers in the provision of palliative and supportive care. To facilitate equitable delivery of supportive care within a pandemic, further research and resources are needed to train and support generalists and palliative care providers. Strategies to successfully collect PROs from all patients in a virtual manner must be developed and implemented.

Challenges in virtual collection of patient-reported data: a prospective cohort study conducted in COVID-19 era.

Prior to the COVID-19 pandemic, patients attending ambulatory clinics at cancer centers in Ontario completed the Edmonton Symptom Assessment Scale (ESAS) at each visit. At our center, completion was via touchpad, with assistance from clinic volunteers. As of March 2020, clinic appointments were conducted virtually when possible and touch pads removed. We anticipated a negative impact on the collection of patient-reported outcomes (PROs) and the recognition of severe symptoms. METHODS: We performed a prospective cross-sectional cohort study to investigate remote ESAS completion by patients with appointments at a weekly surgical oncology clinic. Patients in the initial study cohort were asked to complete and return the ESAS virtually (V). Given low completion rates, the ensuing cohort was asked to complete a hard-copy (HC) ESAS. For the final cohort, we provided remote, personal mentorship by a member of the care team to support virtual electronic ESAS completion (virtual-mentored (VM) cohort). RESULTS: Between May and July 2020, a total of 174 patient encounters were included in the study. For the V cohort, 20/46 patients (44%) successfully completed and returned the electronic ESAS, compared to 49/50 (98%) for the HC cohort. For the VM cohort, the overall completion rate was 74% (58/78); however, 12 of these 58 patients did not independently complete a virtual ESAS. Virtual questionnaire completion was not predicted by age, sex, or tumor site, although patients who completed the ESAS were more likely to be in active management rather than surveillance (p = 0.04). Of all completed forms, 42% revealed a depression score of ≥2, and 27% an anxiety score of ≥4. CONCLUSIONS: We identified significant barriers to the virtual completion of ESAS forms, with a lack of predictive variables. The severe degree of psychological distress reported by ~50% of respondents demonstrates the need for ongoing regular collection/review of these data. Innovative solutions are required to overcome barriers to the virtual collection of PROs.

Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly among histologic types of RPS, with implications for management. The Transatlantic Australasian RPS Working Group (TARPSWG) published a consensus approach to primary RPS, and to complement this, one for recurrent RPS in 2016. Since then, additional studies have been published, and collaborative discussion is ongoing to address the clinical challenges of local recurrence in RPS. METHODS: An extensive literature search was performed, and the previous consensus statements for recurrent RPS were updated after review by TARPSWG members. The search included the most common RPS histologic types: liposarcoma, leiomyosarcoma, solitary fibrous tumor, undifferentiated pleomorphic sarcoma, and malignant peripheral nerve sheath tumor. RESULTS: Recurrent RPS management was evaluated from diagnosis to follow-up evaluation. For appropriately selected patients, resection is safe. Nomograms currently are available to help predict outcome after resection. These and other new findings have been combined with expert recommendations to provide 36 statements, each of which is attributed a level of evidence and grade of recommendation. In this updated document, more emphasis is placed on histologic type and clarification of the intent for surgical treatment, either curative or palliative. Overall, the fundamental tenet of optimal care for patients with recurrent RPS remains individualized treatment after multidisciplinary discussion by an experienced team with expertise in RPS. CONCLUSIONS: Updated consensus recommendations are provided to help guide decision-making for treatment of locally recurrent RPS and better selection of patients who would potentially benefit from surgery.