MRI for Rectal Cancer: Updates and Controversies-AJR Expert Panel Narrative Review.

Rectal MRI is a critical tool in the care of patients with rectal cancer, having established roles for primary staging, restaging, and surveillance. The comprehensive diagnostic and prognostic information provided by MRI helps to optimize treatment decision-making. However, challenges persist in the standardization and interpretation of rectal MRI, particularly in the context of rapidly evolving treatment paradigms, including growing acceptance of nonoperative management. In this AJR Expert Panel Narrative Review, we address recent advances and key areas of contention relating to the use of MRI for rectal cancer. Our objectives include: to discuss concepts regarding anatomic localization of rectal tumors; review the evolving rectal cancer treatment paradigm and implications for MRI assessment; discuss updates and controversies regarding rectal MRI for locoregional staging, restaging, and surveillance; review current rectal MRI acquisition protocols; and discuss challenges in homogenizing and optimizing acquisition parameters.

4th DNA Forensic Symposium: Challenges and future directions in Africa.

The 4th Forensic DNA Symposium in Africa underscored the critical role of regional collaboration in advancing forensic sciences, with a particular focus on forensic DNA examinations, databases, and humanitarian initiatives. The symposium aimed to assess the current forensic DNA capabilities across African countries and develop strategies to expand and better utilize DNA platforms. Key findings from the symposium highlight the necessity for enhanced cooperation among African nations to build robust forensic DNA databases and improve data-sharing mechanisms. The symposium also identified significant gaps in current capabilities and the need to develop legal frameworks, infrastructure, and expertise to support forensic initiatives. Moving forward, these findings suggest a strategic focus on capacity building, establishing standardized procedures, and implementing sustainable forensic practices across the continent. Champions were nominated by attending delegates to lead their respective countries in the implementation of these strategies, marking a critical step towards strengthening forensic science in Africa and addressing the pressing challenges related to crime and humanitarian efforts.

A novel anti-FGFR1 monoclonal antibody OM-RCA-01 exhibits potent antitumor activity and enhances the efficacy of immune checkpoint inhibitors in lung cancer models.

Background: Fibroblast growth factor receptor 1 (FGFR1) plays a crucial role in carcinogenesis. Exploring the combination of the novel humanized monoclonal anti-FGFR1 antibody OM-RCA-01 and immunotherapy was intriguing due to involvement of FGFR1 in mechanisms of resistance to checkpoint inhibitors. Materials and methods: Lung cancer A549, exhibiting distinct levels of FGFR1 expression, were cultured in basic FGF medium with OM-RCA-01 supplementation. The efficacy of antibody monotherapy was validated in a lung cancer xenograft study. To investigate whether OM-RCA-01 could enhance the efficacy of immunotherapy in vitro and in vivo, mixed lymphocyte reaction/Staphylococcal enterotoxin B assays and FGFR1/programmed death-ligand 1-positive patient-derived xenograft model were established. Results: The antibody effectively suppressed receptor phosphorylation, resulting in inhibited cell proliferation. OM-RCA-01 led to a substantial delay in tumor growth compared to non-specific immunoglobulin G in a xenograft study. The median tumor volume was 1048.5 mm3 and 2174 mm3 in the study and vehicle groups, respectively, representing a twofold difference in favor of the anti-FGFR1 antibody. In vitro, the combination of nivolumab and OM-RCA-01 resulted in higher levels of interferon gamma and interleukin-2 release compared with nivolumab alone. In vivo, pembrolizumab in combination with OM-RCA-01 produced a greater inhibitory effect on tumor growth compared with vehicle and pembrolizumab alone. The curve plateaued, indicating minimal tumor growth from day 16 onwards in the combination group. The OM-RCA-01 demonstrated no toxicity, even at therapeutic doses or higher doses. Conclusions: Our preclinical studies demonstrate that OM-RCA-01 exhibits robust activity with minimal toxicity. Combining an anti-FGFR1 antibody with a checkpoint inhibitor may enhance the efficacy of both drugs. However, further studies are needed to elucidate the mechanism of this interaction.

Organ preservation after neoadjuvant long-course chemoradiotherapy versus short-course radiotherapy.

BACKGROUND: Potential differences in organ preservation between total neoadjuvant therapy (TNT) regimens integrating long-course chemoradiotherapy (LCCRT) and short-course radiotherapy (SCRT) in rectal cancer remain undefined. PATIENTS AND METHODS: This natural experiment arose from a policy change in response to the COVID-19 pandemic during which our institution switched from uniformly treating patients with LCCRT to mandating that all patients be treated with SCRT. Our study includes 323 locally advanced rectal adenocarcinoma patients treated with LCCRT-based or SCRT-based TNT from January 2018 to January 2021. Patients who achieved clinical complete response were offered organ preservation with watch-and-wait (WW) management. The primary outcome was 2-year organ preservation. Additional outcomes included local regrowth, distant recurrence, disease-free survival (DFS), and overall survival (OS). RESULTS: Patient and tumor characteristics were similar between LCCRT (n = 247) and SCRT (n = 76) cohorts. Median follow-up was 31 months. Similar clinical complete response rates were observed following LCCRT and SCRT (44.5% versus 43.4%). Two-year organ preservation was 40% [95% confidence interval (CI) 34% to 46%] and 31% (95% CI 22% to 44%) among all patients treated with LCCRT and SCRT, respectively. In patients managed with WW, LCCRT resulted in higher 2-year organ preservation (89% LCCRT, 95% CI 83% to 95% versus 70% SCRT, 95% CI 55% to 90%; P = 0.005) and lower 2-year local regrowth (19% LCCRT, 95% CI 11% to 26% versus 36% SCRT, 95% CI 16% to 52%; P = 0.072) compared with SCRT. The 2-year distant recurrence (10% versus 6%), DFS (90% versus 90%), and OS (99% versus 100%) were similar between WW patients treated with LCCRT and SCRT, respectively. CONCLUSIONS: While WW eligibility was similar between cohorts, WW patients treated with LCCRT had higher 2-year organ preservation and lower local regrowth than those treated with SCRT, yet similar DFS and OS. These data support induction LCCRT followed by consolidation chemotherapy as the preferred TNT regimen for patients with locally advanced rectal cancer pursuing organ preservation.

Colonic Adenosquamous Carcinoma: A Single-Center Review of Patient Clinicopathologic Characteristics, Genetics, and Clinical Outcomes.

(1) Background: Adenosquamous carcinoma (ASC) is a rare subtype of colon cancer. Its rarity makes characterization challenging, although colonic ASC is believed to present at more advanced stages and have worse outcomes versus adenocarcinoma. This study aims to characterize the clinicopathological characteristics and clinical outcomes of colonic ASC. (2) Methods: This is a single-center, retrospective review of patients diagnosed with colonic ASC from 2000 to 2020. Data extracted included patient demographics, staging at diagnosis, tumor clinicopathologic and genetic characteristics, and clinical outcomes. (3) Results: Among 61,126 patients with colorectal cancer, 13 (0.02%) had colonic ASC, with a mean age at diagnosis of 48.7 years. The cecum/ascending colon was the most common primary site (6/13, 46.2%), and all except one patient was diagnosed with Stage III or IV disease. Among the eight patients with mismatch repair genetics available, only one was mismatch repair deficient. Eleven patients (84.6%) underwent surgery, and 11 likewise received some form of chemotherapy. Recurrence occurred in 7 of 13 patients (53.8%), and the overall five-year survival rate was 38.5%. The median survival rate was 39.4 months overall (30.5 months for Stage III, 23.7 months for Stage IV). (4) Conclusions: Overall, colonic ASC is rare, and this cohort of colonic ASC patients demonstrated advanced stage at diagnosis, frequent recurrence, and poor overall survival. Additional research remains to compare these characteristics with those of comparably staged adenocarcinoma and to develop specific management recommendations.

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.

BACKGROUND: 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. METHODS: 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 (50.4-54 Gy) 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. FINDINGS: 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. INTERPRETATION: 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.

Fine mapping of stem rust resistance derived from soft red winter wheat cultivar AGS2000 to an NLR gene cluster on chromosome 6D.

The Puccinia graminis f. sp. tritici (Pgt) Ug99-emerging virulent races present a major challenge to global wheat production. To meet present and future needs, new sources of resistance must be found. Identification of markers that allow tracking of resistance genes is needed for deployment strategies to combat highly virulent pathogen races. Field evaluation of a DH population located a QTL for stem rust (Sr) resistance, QSr.nc-6D from the breeding line MD01W28-08-11 to the distal region of chromosome arm 6DS where Sr resistance genes Sr42, SrCad, and SrTmp have been identified. A locus for seedling resistance to Pgt race TTKSK was identified in a DH population and an RIL population derived from the cross AGS2000 × LA95135. The resistant cultivar AGS2000 is in the pedigree of MD01W28-08-11 and our results suggest that it is the source of Sr resistance in this breeding line. We exploited published markers and exome capture data to enrich marker density in a 10 Mb region flanking QSr.nc-6D. Our fine mapping in heterozygous inbred families identified three markers co-segregating with resistance and delimited QSr.nc-6D to a 1.3 Mb region. We further exploited information from other genome assemblies and identified collinear regions of 6DS harboring clusters of NLR genes. Evaluation of KASP assays corresponding to our co-segregating SNP suggests that they can be used to track this Sr resistance in breeding programs. However, our results also underscore the challenges posed in identifying genes underlying resistance in such complex regions in the absence of genome sequence from the resistant genotypes.

Management of Locally Advanced Rectal Cancer: ASCO Guideline.

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual. ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines.Clinical Practice Guidelines and other guidance ("Guidance") provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by providers and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more.PURPOSETo provide evidence-based guidance for clinicians who treat patients with locally advanced rectal cancer.METHODSA systematic review of the literature published from 2013 to 2023 was conducted to identify relevant systematic reviews, phase II and III randomized controlled trials (RCTs), and observational studies where applicable.RESULTSTwelve RCTs, two systematic reviews, and one nonrandomized study met the inclusion criteria for this systematic review. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.RECOMMENDATIONSFollowing assessment with magnetic resonance imaging, for patients with microsatellite stable or proficient mismatch repair locally advanced rectal cancer, total neoadjuvant therapy (TNT; ie chemoradiation [CRT] and chemotherapy) should be offered as initial treatment for patients with tumors located in the lower rectum and/or patients who are at higher risk for local and/or distant metastases. Patients without higher-risk factors may discuss chemotherapy with selective CRT depending on extent of response, TNT, or neoadjuvant long-course CRT or short-course radiation. For patients who are candidates for TNT, the preferred timing for chemotherapy is after radiation, and neoadjuvant long-course CRT is preferred over short-course radiation therapy (RT), however short-course RT may also be a viable treatment option depending on circumstances. Nonoperative management may be discussed as an alternative to total mesorectal excision for patients who have a clinical complete response to neoadjuvant therapy. For patients whose tumors are microsatellite instability-high or mismatch repair deficient, immunotherapy is recommended.Additional information is available at http://www.asco.org/gastrointestinal-cancer-guidelines.

Clinical Calculator for Predicting Freedom From Recurrence After Resection of Stage I-III Colon Cancer in Patients With Microsatellite Instability.

PURPOSE: Outcome for patients with nonmetastatic, microsatellite instability (MSI) colon cancer is favorable: however, high-risk cohorts exist. This study was aimed at developing and validating a nomogram model to predict freedom from recurrence (FFR) for patients with resected MSI colon cancer. PATIENTS AND METHODS: Data from patients who underwent curative resection of stage I, II, or III MSI colon cancer in 2014-2021 (model training cohort, 384 patients, 33 events; median follow-up, 38.8 months) were retrospectively collected from institutional databases. Variables associated with recurrence in multivariable analysis were selected for inclusion in the clinical calculator. The calculator's predictive accuracy was measured with the concordance index and validated using data from patients who underwent treatment for MSI colon cancer in 2007-2013 (validation cohort, 164 patients, eight events; median follow-up, 84.8 months). RESULTS: T category and number of positive lymph nodes were significantly associated with recurrence in multivariable analysis and were selected for inclusion in the clinical calculator. The calculator's concordance index for FFR in the model training cohort was 0.812 (95% CI, 0.742 to 0.873), compared with 0.759 (95% CI, 0.683 to 0.840) for the staging schema of the eighth edition of the American Joint Committee on Cancer Staging Manual. The concordance index for the validation cohort was 0.744 (95% CI, 0.666 to 0.822), confirming robust predictive accuracy. CONCLUSION: Although in general patients with nonmetastatic MSI colon cancer had favorable outcome, patients with advanced T category and multiple metastatic lymph nodes had higher risk of recurrence. The clinical calculator identified patients with MSI colon cancer at high risk for recurrence, and this could inform surveillance strategies. In addition, the model could be used in trial design to identify patients suitable for novel adjuvant therapy.

Development and evaluation of the Capability, Opportunity, and Motivation to deliver Physical Activity in School Scale (COM-PASS).

BACKGROUND: Teachers are recognized as 'key agents' for the delivery of physical activity programs and policies in schools. The aim of our study was to develop and evaluate a tool to assess teachers' capability, opportunity, and motivation to deliver school-based physical activity interventions. METHODS: The development and evaluation of the Capability, Opportunity, and Motivation to deliver Physical Activity in School Scale (COM-PASS) involved three phases. In Phase 1, we invited academic experts to participate in a Delphi study to rate, provide recommendations, and achieve consensus on questionnaire items that were based on the Capability, Opportunity, and Motivation Behavior (COM-B) model. Each item was ranked on the degree to which it matched the content of the COM-B model, using a 5-point scale ranging from '1 = Poor match' to '5 = Excellent match'. In Phase 2, we interviewed primary and secondary school teachers using a 'think-aloud' approach to assess their understanding of the items. In Phase 3, teachers (n = 196) completed the COM-PASS to assess structural validity using confirmatory factor analysis (CFA). RESULTS: Thirty-eight academic experts from 14 countries completed three rounds of the Delphi study. In the first round, items had an average rating score of 4.04, in the second round 4.51, and in the third (final) round 4.78. The final tool included 14 items, which related to the six constructs of the COM-B model: physical capability, psychological capability, physical opportunity, social opportunity, reflective motivation, and automatic motivation. In Phase 2, ten teachers shared their interpretation of COM-PASS via a 20-min interview, which resulted in minor changes. In Phase 3, CFA of the 3-factor model (i.e., capability, opportunity, and motivation) revealed an adequate fit to the data (χ2 = 122.6, p < .001, CFI = .945, TLI = .924, RMSEA = .066). The internal consistencies of the three subscale scores were acceptable (i.e., capability: α = .75, opportunity: α = .75, motivation: α = .81). CONCLUSION: COM-PASS is a valid and reliable tool for assessing teachers' capability, opportunity, and motivation to deliver physical activity interventions in schools. Further studies examining additional psychometric properties of the COM-PASS are warranted.

Comparison of perioperative outcomes between colorectal operations performed on weekends vs those performed on weekdays.

BACKGROUND: Weekend surgical time is an underused asset. Concerns over a possible weekend effect (substandard care) may be a barrier. METHODS: This study examined whether a weekend effect applies to elective colorectal surgery via a single-center retrospective analysis comparing outcomes between patients who underwent elective colorectal surgery on a weekend vs a weekday. Demographics, length of stay (LOS), operative and anesthesia time, the rate of reoperation within 30 days, and the rate of major complications were compared between patient groups. RESULTS: Of the 2008 patients identified, 1721 (85.7%) underwent surgery on a weekday, and 287 (14.3%) underwent surgery on a weekend. The proportion of operations with an open approach was higher on weekends than weekdays (49.5% vs 41.8%, P = .017). Patients who underwent surgery on the weekend tended to have a shorter mean (SE) for LOS (4.2 [0.2] vs 6.1 [0.2], P < .001), anesthesia time (233.8 [6.5] vs 307.6 [3.3] minutes, P < .001), and operative time (225.4 [6.4] vs. 297.6 [3.3] minutes, P < .001). On multivariable analysis, patients who had an operation on a weekend had a 38% lower chance of having a prolonged LOS (>75th percentile of LOS) compared with those who had an operation on a weekday (adjusted odds ratio = 0.62; 95% CI 0.42-0.92). There were no differences in rates of complications or reoperation for patients undergoing surgery on a weekend compared with a weekday. CONCLUSION: At centers with experienced anesthesiologists, appropriately trained nursing staff, and expert surgeons, colorectal surgery performed on a weekend has similar safety outcomes as surgeries performed on a weekday.

Contrasting association pattern of plasma low-density lipoprotein with white matter integrity in APOE4 carriers versus non-carriers.

Apolipoprotein E ε4 (APOE4) is a strong genetic risk factor of Alzheimer's disease and metabolic dysfunction. However, whether APOE4 and markers of metabolic dysfunction synergistically impact the deterioration of white matter (WM) integrity in older adults remains unknown. In the UK Biobank data, we conducted a multivariate analysis to investigate the interactions between APOE4 and 249 plasma metabolites (measured using nuclear magnetic resonance spectroscopy) with whole-brain WM integrity (measured by diffusion-weighted magnetic resonance imaging) in a cohort of 1917 older adults (aged 65.0-81.0 years; 52.4 % female). Although no main association was observed between either APOE4 or metabolites with WM integrity (adjusted P > 0.05), significant interactions between APOE4 and metabolites with WM integrity were identified. Among the examined metabolites, higher concentrations of low-density lipoprotein and very low-density lipoprotein were associated with a lower level of WM integrity (b=-0.12, CI=-0.14,-0.10) among APOE4 carriers. Conversely, among non-carriers, they were associated with a higher level of WM integrity (b=0.05, CI=0.04,0.07), demonstrating a significant moderation role of APOE4 (b =-0.18, CI=-0.20,-0.15, P<0.00001).

Ice sheet-free West Antarctica during peak early Oligocene glaciation.

One of Earth's most fundamental climate shifts, the greenhouse-icehouse transition 34 million years ago, initiated Antarctic ice sheet buildup, influencing global climate until today. However, the extent of the ice sheet during the Early Oligocene Glacial Maximum (~33.7 to 33.2 million years ago) that immediately followed this transition-a critical knowledge gap for assessing feedbacks between permanently glaciated areas and early Cenozoic global climate reorganization-is uncertain. In this work, we present shallow-marine drilling data constraining earliest Oligocene environmental conditions on West Antarctica's Pacific margin-a key region for understanding Antarctic ice sheet evolution. These data indicate a cool-temperate environment with mild ocean and air temperatures that prevented West Antarctic Ice Sheet formation. Climate-ice sheet modeling corroborates a highly asymmetric Antarctic ice sheet, thereby revealing its differential regional response to past and future climatic change.

Discovery and validation of a 10-gene predictive signature for response to adjuvant chemotherapy in stage II and III colon cancer.

Identifying patients with stage II and III colon cancer who will benefit from 5-fluorouracil (5-FU)-based adjuvant chemotherapy is crucial for the advancement of personalized cancer therapy. We employ a semi-supervised machine learning approach to analyze a large dataset with 933 stage II and III colon cancer samples. Our analysis leverages gene regulatory networks to discover an 18-gene prognostic signature and to explore a 10-gene signature that potentially predicts chemotherapy benefits. The 10-gene signature demonstrates strong prognostic power and shows promising potential to predict chemotherapy benefits. We establish a robust clinical assay on the NanoString nCounter platform, validated in a retrospective formalin-fixed paraffin-embedded (FFPE) cohort, which represents an important step toward clinical application. Our study lays the groundwork for improving adjuvant chemotherapy and potentially expanding into immunotherapy decision-making in colon cancer. Future prospective studies are needed to validate and establish the clinical utility of the 10-gene signature in clinical settings.

Exercise and Protection from Age-Related Cognitive Decline.

In this chapter, we review the cross-sectional evidence in healthy human subjects for physical activity and cardiorespiratory fitness to offer neuroprotection and moderate cognitive decline in older age. The role of exercise training on cognition in healthy older adults and those diagnosed with mild cognitive impairment (MCI) is also discussed, including the evidence from neuroimaging studies that document changes to brain structure and function after a period of exercise training and improved fitness. Finally, in reference to animal models, the potential neurophysiological mechanisms for physical activity and exercise to impact human brain health are highlighted.

The role of placental kisspeptin in trophoblast invasion and migration: an assessment in Kiss1r knockout mice, BeWo cell lines and human term placenta.

Context There is mounting evidence implicating kisspeptin signalling in placental development and function. Aims This study aimed to elucidate kisspeptin's role in trophoblast invasion and migration using three experimental models. Methods First, we examined the mouse fetus and placenta in a kisspeptin receptor (Kiss1r) knockout (KO) model. Fetal/placental weights and gene expression (quantitative polymerase chain reaction) were assessed. Second, we determined kisspeptin effects on a human trophoblast (BeWo) cell line in vitro . Third, we examined KISS1 and KISS1R gene expression in human placenta from term and pre-term pregnancies. Key results No difference was found in fetal or placental weight between Kiss1r KO and wildtype mice. However, expression of the trophoblast invasion marker, Mmp2 mRNA, was greater in the placental labyrinth zone of Kiss1r KO mice. BeWo cell models of villus cytotrophoblast and syncytiotrophoblast cells exhibited kisspeptin protein expression, with greater expression in syncytiotrophoblast, consistent with KISS1 mRNA. Kisspeptin treatment inhibited the migratory potential of cytotrophoblast-like cells. Finally, while no difference was seen in KISS1 and KISS1R mRNA between term and pre-term placentas, we saw a difference in the relative expression of each gene pre-term. We also observed a positive correlation between KISS1 expression and maternal body mass index. Conclusions Our results indicate that kisspeptin may inhibit trophoblast invasion. Implications Further investigation is required to clarify specific regulatory mechanisms.

Alliance A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer.

BACKGROUND: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after TNT may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. METHODS: In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N +) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N + vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long-course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (± 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 312 evaluable patients (156 per arm) will provide statistical power of 90.5% to detect a 17% increase in cCR rate, at a one-sided alpha = 0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse event rates. Biospecimens including archival tumor tissue, plasma and buffy coat, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and had accrued 330 patients as of May 2024. Study support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . DISCUSSION: Building on data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed The Janus Rectal Cancer Trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT05610163; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

Mimics of primary ovarian cancer and primary peritoneal carcinomatosis - A pictorial review.

Numerous conditions can mimic ovarian malignancy. Identifying the origin of a pelvic mass or disseminated peritoneal abnormality on imaging is important to ensure that the patient receives optimal management by the appropriate clinical team. Ovarian cancer mimics include infections and other neoplastic processes, for example, actinomycosis, lymphoma, and sarcoma. We will illustrate intraperitoneal and extraperitoneal ovarian and non-ovarian mimics. Primary peritoneal carcinomatosis mimics include processes such as deep infiltrating endometriosis and rare causes such as gliomatosis peritonei and diffuse peritoneal leiomyomatosis. We aim to illustrate the multimodality key imaging appearances of common and rarer types of mimics.

Watch and Wait in Rectal Cancer Patients with Residual Mucin on MRI following Neoadjuvant Therapy.

BACKGROUND: Neoadjuvant therapy (NAT) leads to a clinical complete response (cCR) in a significant proportion of patients with locally advanced rectal cancer (LARC), allowing for possible nonoperative management. The presence of mucin on MRI after NAT leads to uncertainty about residual disease and appropriateness of a watch-and-wait (WW) strategy in patients with no evidence of disease on proctoscopy (endoscopic cCR). METHODS: MRI reports for LARC patients seen between July 2016 and January 2020 at Memorial Sloan Kettering Cancer Center were queried for presence of mucin in the tumor bed on MRI following NAT. Clinicodemographic, pathologic, and outcome data were compiled and analyzed. RESULTS: Of 71 patients with mucin on post-treatment MRI, 20 had a cCR and 51 had abnormalities on endoscopy and/or physical exam. One patient with a cCR opted out of WW; thus, 19 patients (27%) entered WW and 52 patients (73%) were planned for surgery (Non-WW). Of the 19 WW patients, 15 (79%) have had no local regrowth with median follow-up of 50 months (range, 29-76 months), while 4 (21%) experienced regrowth between 9 and 29 months after neoadjuvant therapy. Of the 52 patients who were planned to have surgery (Non-WW), 49 underwent resection while 3 developed metastatic disease that precluded curative-intent surgery. Five (10%) of the 49 patients who underwent surgery, including the one with an endoscopic cCR, had a pathologic complete response. CONCLUSIONS: The presence of mucin after NAT for LARC does not preclude WW management in otherwise appropriate candidates who achieve an endoscopic cCR.