Smoking-associated gene expression alterations in nasal epithelium reveal immune impairment linked to lung cancer risk.

BACKGROUND: Lung cancer is the leading cause of cancer-related death in the world. In contrast to many other cancers, a direct connection to modifiable lifestyle risk in the form of tobacco smoke has long been established. More than 50% of all smoking-related lung cancers occur in former smokers, 40% of which occur more than 15 years after smoking cessation. Despite extensive research, the molecular processes for persistent lung cancer risk remain unclear. We thus set out to examine whether risk stratification in the clinic and in the general population can be improved upon by the addition of genetic data and to explore the mechanisms of the persisting risk in former smokers. METHODS: We analysed transcriptomic data from accessible airway tissues of 487 subjects, including healthy volunteers and clinic patients of different smoking statuses. We developed a computational model to assess smoking-associated gene expression changes and their reversibility after smoking is stopped, comparing healthy subjects to clinic patients with and without lung cancer. RESULTS: We find persistent smoking-associated immune alterations to be a hallmark of the clinic patients. Integrating previous GWAS data using a transcriptional network approach, we demonstrate that the same immune- and interferon-related pathways are strongly enriched for genes linked to known genetic risk factors, demonstrating a causal relationship between immune alteration and lung cancer risk. Finally, we used accessible airway transcriptomic data to derive a non-invasive lung cancer risk classifier. CONCLUSIONS: Our results provide initial evidence for germline-mediated personalized smoke injury response and risk in the general population, with potential implications for managing long-term lung cancer incidence and mortality.

Analysis of domain shift in whole prostate gland, zonal and lesions segmentation and detection, using multicentric retrospective data.

Despite being one of the most prevalent forms of cancer, prostate cancer (PCa) shows a significantly high survival rate, provided there is timely detection and treatment. Computational methods can help make this detection process considerably faster and more robust. However, some modern machine-learning approaches require accurate segmentation of the prostate gland and the index lesion. Since performing manual segmentations is a very time-consuming task, and highly prone to inter-observer variability, there is a need to develop robust semi-automatic segmentation models. In this work, we leverage the large and highly diverse ProstateNet dataset, which includes 638 whole gland and 461 lesion segmentation masks, from 3 different scanner manufacturers provided by 14 institutions, in addition to other 3 independent public datasets, to train accurate and robust segmentation models for the whole prostate gland, zones and lesions. We show that models trained on large amounts of diverse data are better at generalizing to data from other institutions and obtained with other manufacturers, outperforming models trained on single-institution single-manufacturer datasets in all segmentation tasks. Furthermore, we show that lesion segmentation models trained on ProstateNet can be reliably used as lesion detection models.

Imaging of pancreatic ductal adenocarcinoma - An update for all stages of patient management.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a common and lethal cancer. From diagnosis to disease staging, response to neoadjuvant therapy assessment and patient surveillance after resection, imaging plays a central role, guiding the multidisciplinary team in decision-planning. Review aims and findings: This review discusses the most up-to-date imaging recommendations, typical and atypical findings, and issues related to each step of patient management. Example cases for each relevant condition are presented, and a structured report for disease staging is suggested. Conclusion: Despite current issues in PDAC imaging at different stages of patient management, the radiologist is essential in the multidisciplinary team, as the conveyor of relevant imaging findings crucial for patient care.

Local Regrowth and the Risk of Distant Metastases Among Patients Undergoing Watch-and-Wait for Rectal Cancer: What Is the Best Control Group? Multicenter Retrospective Study.

BACKGROUND: A proportion of rectal cancer patients who achieve a clinical complete response may develop local regrowth. Although salvage appears to provide appropriate local control, the risk of distant metastases is less known. OBJECTIVE: To compare the risk of distant metastases between patients who achieve a clinical complete response (watch-and-wait strategy) and subsequent local regrowth and patients managed by surgery after chemoradiation. DESIGN: Retrospective multicenter cohort study. SETTINGS: This study used data of patients from 3 institutions who were treated between 1993 and 2019. PATIENTS: Patients with initial clinical complete response (after neoadjuvant therapy) followed by local regrowth and patients with near-complete pathological response (≤10%) after straightforward surgery after chemoradiation were included. MAIN OUTCOME MEASURES: Univariate and multivariate analyses were performed to identify risk factors for distant metastases. Kaplan-Meier curves were created (log-rank test) to compare survival outcomes. Analyses were performed using time zero as last day of radiation therapy or as date of salvage resection in the local regrowth group. RESULTS: Twenty-one of 79 patients with local regrowth developed distant metastases, whereas only 10 of 74 after upfront total mesorectal excision following neoadjuvant chemoradiation therapy ( p = 0.04). Local regrowth and final pathology (ypT3-4) were the only independent risk factors associated with distant metastases. When using date of salvage resection as time zero, distant metastases-free survival rates were significantly inferior for patients with local regrowth (70% vs 86%; p = 0.01). LIMITATIONS: Small number of patients, many neoadjuvant therapies, and selection bias. CONCLUSIONS: Patients undergoing watch-and-wait strategy who develop local regrowth are at higher risk for development of distant metastases compared to patients with near-complete pathological response managed by upfront surgery after chemoradiation. See Video Abstract. NUEVO CRECIMIENTO LOCAL Y EL RIESGO DE METSTASIS A DISTANCIA ENTRE PACIENTES SOMETIDOS A OBSERVACIN Y ESPERA POR CNCER DE RECTO CUL ES EL MEJOR GRUPO DE CONTROL ESTUDIO RETROSPECTIVO MUTICNTRICO: ANTECEDENTES:Una proporción de pacientes que logran una respuesta clínica completa pueden desarrollar un nuevo crecimiento local. Si bien el rescate parece proporcionar un control local apropiado, el riesgo de metástasis a distancia es menos conocido.OBJETIVO:Comparar el riesgo de metástasis a distancia entre los pacientes que logran una respuesta clínica completa (estrategia de observación y espera) y el nuevo crecimiento local posterior con los pacientes tratados con cirugía después de la quimiorradiación.DISEÑO:Estudio de cohorte multicéntrico retrospectivo.CONFIGURACIÓN:Este estudio utilizó datos de pacientes de 3 instituciones que fueron tratados entre 1993 y 2019.PACIENTES:Pacientes con respuesta clínica completa inicial (después de la terapia neoadyuvante) seguida de crecimiento local nuevo y pacientes con respuesta patológica casi completa (≤10 %) después de cirugía directa después de quimiorradiación.PRINCIPALES MEDIDAS DE RESULTADO:Se realizó un análisis univariante/multivariante para identificar los factores de riesgo de metástasis a distancia. Se crearon curvas de Kaplan-Meier (prueba de rango logarítmico) para comparar los resultados de supervivencia. El análisis se realizó utilizando el tiempo cero como último día de radioterapia (1) o como fecha de resección de rescate (2) en el grupo de recrecimiento local.RESULTADOS:Veintiuno de 79 pacientes con recrecimiento local desarrollaron metástasis a distancia, mientras que solo 10 de 74 después de una cirugía sencilla (p = 0,04). El recrecimiento local y la patología final (ypT3-4) fueron los únicos factores de riesgo independientes asociados con las metástasis a distancia. Cuando se utilizó la fecha de la resección de rescate como tiempo cero, las tasas de supervivencia sin metástasis a distancia fueron significativamente inferiores para los pacientes con recrecimiento local (70 frente a 86 %; p = 0,01).LIMITACIONES:Pequeño número de pacientes, muchas terapias neoadyuvantes, sesgo de selección.CONCLUSIONES:Los pacientes sometidos a observación y espera que desarrollan un nuevo crecimiento local tienen un mayor riesgo de desarrollar metástasis a distancia en comparación con los pacientes con una respuesta patológica casi completa manejados con cirugía por adelantado después de la quimiorradiación. (Traducción-Dr. Xavier Delgadillo ).

Watch and Wait for rectal cancer in inflammatory bowel disease.

Colorectal cancer is currently the third most frequently diagnosed type of cancer and the second cause of cancer death in the western world. Inflammatory bowel disease patients are 2-6 times more likely to develop CRC than the general population. Patients with CRC arising through Inflammatory Bowel Disease have an indication for surgery. However, in patients without Inflammatory Bowel Disease, the use of organ (rectum) preservation strategies after neoadjuvant treatment is on the rise, which means that patients are able to keep the organ without the need for complete excision, either by treatment with radiotherapy and chemotherapy, or in combination with endoscopic or surgical techniques that allow local excision without the need for resection of the entire organ. The patient management approach known as the Watch and Wait programme was first introduced in 2004 by a team from São Paulo, Brazil. This approach suggested that patients who had an excellent or complete clinical response after neoadjuvant treatment could defer surgery and instead undergo Watch and Wait. This organ preservation technique became popular because it allowed patients to avoid the complications associated with major surgery while achieving similar oncological outcomes to those who underwent both neoadjuvant therapy and radical surgery. Following completion of neoadjuvant treatment, a decision to defer surgery is made based on whether a clinical Complete Response can be achieved, which means there is no evidence of tumour in clinical and radiological examination. The International Watch and Wait Database has published long-term oncological outcomes for patients treated with this strategy, and more patients are showing interest in this treatment option. However, it is important to note that up to 1/3 of patients selected for Watch and Wait may eventually require surgery for local regrowth (also known as 'deferred definitive surgery') at any time during follow-up after an initial 'apparent' clinical Complete Response. Compliance with a strict surveillance protocol ensures early detection of regrowth, which is usually amenable to R0 surgery and provides excellent long-term local disease control. Nonetheless, it is crucial to assess the perioperative consequences of having surgery for regrowth later and whether there are any negative effects from deferring surgery. Currently, the Watch and Wait strategy is recommended in the NCCN guidelines for clinical complete responders and only in specialised multidisciplinary centres.There is no case in the literature that portrays the use of the Watch and Wait programme for patients with inflammatory bowel disease and rectal cancer.The authors intend to present a case that demonstrates the difficulties in the assessment of patients with inflammatory bowel disease, the risks of using radiotherapy in this patients and the challenges of surveillance for patients with colorectal cancer and inflammatory bowel disease.

Data-Driven Medicine in the Diagnosis and Treatment of Infertility.

Infertility, although not a life-threatening condition, affects around 15% of couples trying for a pregnancy. The increasing availability of large datasets from various sources, together with advances in machine learning (ML) and artificial intelligence (AI), are enabling a transformational change in infertility care. However, real-world applications of data-driven medicine in infertility care are still relatively limited. At present, very little can prevent infertility from arising; more work is required to learn about ways to improve natural conception and the detection and diagnosis of infertility, improve assisted reproduction treatments (ART) and ultimately develop useful clinical-decision support systems to assure the successful outcome of either fertility preservation or infertility treatment. In this opinion article, we discuss recent influential work on the application of big data and AI in the prevention, diagnosis and treatment of infertility. We evaluate the challenges of the sector and present an interpretation of the different innovation forces that are driving the emergence of a systems approach to infertility care. Efforts including the integration of multi-omics information, collection of well-curated biological samples in specialised biobanks, and stimulation of the active participation of patients are considered. In the era of Big Data and AI, there is now an exciting opportunity to leverage the progress in genomics and digital technologies and develop more sophisticated approaches to diagnose and treat infertility disorders.

Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer.

Chromosomal instability is a major challenge to patient stratification and targeted drug development for high-grade serous ovarian carcinoma (HGSOC). Here we show that somatic copy number alterations (SCNAs) in frequently amplified HGSOC cancer genes significantly correlate with gene expression and methylation status. We identify five prevalent clonal driver SCNAs (chromosomal amplifications encompassing MYC, PIK3CA, CCNE1, KRAS and TERT) from multi-regional HGSOC data and reason that their strong selection should prioritise them as key biomarkers for targeted therapies. We use primary HGSOC spheroid models to test interactions between in vitro targeted therapy and SCNAs. MYC chromosomal copy number is associated with in-vitro and clinical response to paclitaxel and in-vitro response to mTORC1/2 inhibition. Activation of the mTOR survival pathway in the context of MYC-amplified HGSOC is statistically associated with increased prevalence of SCNAs in genes from the PI3K pathway. Co-occurrence of amplifications in MYC and genes from the PI3K pathway is independently observed in squamous lung cancer and triple negative breast cancer. In this work, we show that identifying co-occurrence of clonal driver SCNA genes could be used to tailor therapeutics for precision medicine.

Imaging standardisation in metastatic colorectal cancer: A joint EORTC-ESOI-ESGAR expert consensus recommendation.

BACKGROUND: Treatment monitoring in metastatic colorectal cancer (mCRC) relies on imaging to evaluate the tumour burden. Response Evaluation Criteria in Solid Tumors provide a framework on reporting and interpretation of imaging findings yet offer no guidance on a standardised imaging protocol tailored to patients with mCRC. Imaging protocol heterogeneity remains a challenge for the reproducibility of conventional imaging end-points and is an obstacle for research on novel imaging end-points. PATIENTS AND METHODS: Acknowledging the recently highlighted potential of radiomics and artificial intelligence tools as decision support for patient care in mCRC, a multidisciplinary, international and expert panel of imaging specialists was formed to find consensus on mCRC imaging protocols using the Delphi method. RESULTS: Under the guidance of the European Organisation for Research and Treatment of Cancer (EORTC) Imaging and Gastrointestinal Tract Cancer Groups, the European Society of Oncologic Imaging (ESOI) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the EORTC-ESOI-ESGAR core imaging protocol was identified. CONCLUSION: This consensus protocol attempts to promote standardisation and to diminish variations in patient preparation, scan acquisition and scan reconstruction. We anticipate that this standardisation will increase reproducibility of radiomics and artificial intelligence studies and serve as a catalyst for future research on imaging end-points. For ongoing and future mCRC trials, we encourage principal investigators to support the dissemination of these imaging standards across recruiting centres.

Zebrafish Avatars of rectal cancer patients validate the radiosensitive effect of metformin.

Neoadjuvant chemoradiation (nCRT) followed by surgery represents the standard of care in patients with locally advanced rectal cancer. Increasing radiotherapy (RT) doses and chemotherapy cycles with 5FU have been associated with increased rates of complete response, however these strategies imply significant toxicity. In the last years, epidemiologic findings have demonstrated that metformin is associated with significantly higher rates of pathological complete response to nCRT. Also, pre-clinical studies using cell lines provide evidence for the radiosensitive effect of metformin. However, no studies have been performed using rectal cancer patient samples to test this radiosensitive effect of metformin and compared it to the standard 5FU. Here, we designed an experimental study to compare both radiosensitizers in the zebrafish xenograft model (zAvatar), using rectal cancer surgical specimens and diagnostic biopsies. Patient zAvatars confirmed that metformin has indeed a powerful in vivo radiosensitizer effect, similar to 5FU. Our work confirms that metformin constitutes a promising less toxic alternative to the standard 5FU, which could be game changing in elderly/frail patients to optimize tumor regression.

Re-staging and follow-up of rectal cancer patients with MR imaging when "Watch-and-Wait" is an option: a practical guide.

In the past nearly 20 years, organ-sparing when no apparent viable tumour is present after neoadjuvant therapy has taken an increasingly relevant role in the therapeutic management of locally-advanced rectal cancer patients. The decision to include a patient or not in a "Watch-and-Wait" program relies mainly on endoscopic assessment by skilled surgeons, and MR imaging by experienced radiologists. Strict surveillance using the same modalities is required, given the chance of a local regrowth is of approximately 25-30%, almost always surgically salvageable if caught early. Local regrowths occur at the endoluminal aspect of the primary tumour bed in almost 90% of patients, but the rest are deep within it or outside the rectal wall, in which case detection relies solely on MR Imaging. In this educational review, we provide a practical guide for radiologists who are, or intend to be, involved in the re-staging and follow-up of rectal cancer patients in institutions with an established "Watch-and-Wait" program. First, we discuss patient preparation and MR imaging acquisition technique. Second, we focus on the re-staging MR imaging examination and review the imaging findings that allow us to assess response. Third, we focus on follow-up assessments of patients who defer surgery and confer about the early signs that may indicate a sustained/non-sustained complete response, a rectal/extra-rectal regrowth, and the particular prognosis of the "near-complete" responders. Finally, we discuss our proposed report template.

Pancreatic intraductal papillary mucinous neoplasm associated colloid carcinoma.

Colloid carcinomas are rare pancreatic tumors characterized by the presence of mucin pools with scarce malignant cells. Most of these neoplasms arise from intestinal-type intraductal papillary mucinous neoplasms (IPMNs). We report a case of a 77-year-old male patient who presented with weight loss, asthenia, lumbar pain and diabetes. Imaging studies revealed a mixed-type IPMN with high-risk features and a possible invasive component. The patient underwent surgical resection and the histology confirmed an invasive colloid carcinoma of the pancreas associated with an intestinal-type IPMN. Although invasive ductal and colloid carcinomas may look similar on imaging studies, its distinction is important because the latter have a better prognosis.

Early conformational changes at tumour bed and long term response after neoadjuvant therapy in locally-advanced rectal cancer.

OBJECTIVES: To evaluate how changes in tumour scar depth angle and thickness in the post-neoadjuvant period relate to long-term response in locally-advanced rectal cancer patients. METHODS: Informed consent was obtained from all patients and institutional review board approved this retrospective study. Sixty-nine consecutive locally-advanced rectal cancer patients who underwent neoadjuvant therapy and were selected for "Watch-and-Wait" were enrolled. Two radiologists, O1 and O2, blindly and independently reviewed the 1st and 2nd post-neoadjuvant therapy pelvic MRI T2-weighted images and recorded depth angle and thickness of the tumour scar. Value changes were calculated by simple subtraction (2nd-1st). Mann-Whitney U test was employed to assess for significant differences between sustained clinical complete responders (SCR), defined as patients with pathologic complete response or clinical complete response with a minimum follow-up of 1 year; and non-sustained complete responders (non-SCR). Interobserver agreement was estimated using intraclass correlation coefficient (ICC). Data on mrTRG, DWI and endoscopy at 1st and 2nd timepoints were retrieved for comparison. RESULTS: In SCR, depth angle change between 1st (med = 10 weeks after end of radiotherapy) and 2nd (med = 23 weeks after end of radiotherapy) timepoints was significantly different (O1:p = 0.004; O2:p = 0.010): the SCR group showed a depth angle reduction (O1:med=-4.45; O2:med=-2.35), whereas non-SCRs showed a depth angle increase (O1:med=+2.60; O2:med=+7.40). Also, at 2nd timepoint, SCR scars were significantly thinner both for O1 (p = 0.003; SCR:med = 7.05 mm; non-SCR:med = 9.4 mm) and O2 (p = 0.006; SCR:med = 6.45 mm; non-SCR:med = 8.2 mm). A depth angle increase >21º between 1st and 2nd timepoints and a scar thickness >10 mm at 2nd timepoint were not sensitive but were highly specific for a non-SCR (91/94 %) for both observers. Interobserver agreement was good for scar depth angle change (ICC = 0.65) and excellent for scar thickness at 2nd timepoint (ICC = 0.84). Of the retrieved data, only DWI at 2nd timepoint was discriminative (p = 0.043) providing a similar sensitivity (33 %) and a slightly lower specificity (87.5 %). CONCLUSION: Tumour scar expansion >21° between 1st and 2nd post-neoadjuvancy MRI and a scar thickness >10 mm at 2nd post-neoadjuvancy MRI may consistently indicate a non-SCR with high specificity in locally-advanced rectal cancer patients.

Safety and Efficacy of Virtual Prostatectomy With Single-Dose Radiotherapy in Patients With Intermediate-Risk Prostate Cancer: Results From the PROSINT Phase 2 Randomized Clinical Trial.

IMPORTANCE: Ultra-high single-dose radiotherapy (SDRT) represents a potential alternative to curative extreme hypofractionated stereotactic body radiotherapy (SBRT) in organ-confined prostate cancer. OBJECTIVE: To compare toxic effect profiles, prostate-specific antigen (PSA) responses, and quality-of-life end points of SDRT vs extreme hypofractionated SBRT. DESIGN, SETTING, AND PARTICIPANTS: The PROSINT single-institution phase 2 randomized clinical trial accrued, between September 2015 and January 2017, 30 participants with intermediate-risk prostate cancer to receive SDRT or extreme hypofractionated SBRT. Androgen deprivation therapy was not permitted. Data were analyzed from March to May 2020. INTERVENTIONS: Patients were randomized in a 1:1 ratio to receive 5 × 9 Gy SBRT (control arm) or 24 Gy SDRT (test arm). MAIN OUTCOMES AND MEASURES: The primary end point was toxic effects; the secondary end points were PSA response, PSA relapse-free survival, and patient-reported quality of life measured with the International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC)-26 questionnaires. RESULTS: A total of 30 men were randomized; median (interquartile range) age was 66.3 (61.2-69.9) and 73.6 (64.7-75.9) years for the SBRT and SDRT arms, respectively. Time to appearance and duration of acute and late toxic effects were similar in the 2 trial arms. Cumulative late actuarial urinary toxic effects did not differ for grade 1 (hazard ratio [HR], 0.41; 90% CI, 0.13-1.27) and grade 2 or greater (HR, 1.07; 90% CI, 0.21-5.57). Actuarial grade 1 late gastrointestinal (GI) toxic effects were comparable (HR, 0.37; 90% CI, 0.07-1.94) and there were no grade 2 or greater late GI toxic effects. Declines in PSA level to less than 0.5 ng/mL occurred by 36 months in both study arms. No PSA relapses occurred in favorable intermediate-risk disease, while in the unfavorable category, the actuarial 4-year PSA relapse-free survival values were 75.0% vs 64.0% (HR, 0.76; 90% CI, 0.17-3.31) for SBRT vs SDRT, respectively. The EPIC-26 median summary scores for the genitourinary and GI domains dropped transiently at 1 month and returned to pretreatment scores by 3 months in both arms. The IPSS-derived transient late urinary flare symptoms occurred at 9 to 18 months in 20% (90% CI, 3%-37%) of patients receiving SDRT. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial among patients with intermediate-risk prostate cancer, SDRT was safe and associated with low toxicity, and the tumor control and quality-of-life end points closely match the SBRT arm outcomes. Further studies are encouraged to explore indications for SDRT in the cure of prostate cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02570919.

MRI of rectal cancer-relevant anatomy and staging key points.

Rectal cancer has the eighth highest cancer incidence worldwide, and it is increasing in young individuals. However, in countries with a high human development index, mortality is decreasing, which may reflect better patient management, imaging being key. We rely on imaging to establish the great majority of clinical tumour features for therapeutic decision-making, namely tumour location, depth of invasion, lymph node involvement, circumferential resection margin status and extramural venous invasion. Despite major improvements in technique resulting in better image quality, and notwithstanding the dissemination of guidelines and examples of standardised reports, rectal cancer staging is still challenging on the day-to-day practice, and we believe there are three reasons. First, the normal posterior pelvic compartment anatomy and variants are not common knowledge to radiologists; second, not all rectal cancers fit in review paper models, namely the very early, the very low and the mucinous; and third, the key clinical tumour features may be tricky to analyse. In this review, we discuss the normal anatomy of the rectum and posterior compartment of the pelvis, systematise all rectal cancer staging key points and elaborate on the particularities of early, low and mucinous tumours. We also include our suggested reporting templates and a discussion of its comparison to the reporting templates provided by ESGAR and SAR.

Salvage Surgery With Organ Preservation for Patients With Local Regrowth After Watch and Wait: Is It Still Possible?

BACKGROUND: Patients with rectal cancer who achieve complete clinical response after neoadjuvant chemoradiation have been managed nonoperatively. Thirty percent of these patients may develop a local regrowth, and salvage resection with radical surgery is usually recommended. However, selected patients could be offered additional organ preservation by local excision. We hypothesized that patients with baseline T2 who underwent neoadjuvant therapy (for the specific purpose of achieving a complete clinical response) were more likely to harbor recurrent disease at an earlier stage and amenable to organ preservation strategies (local excision) when compared with T3/T4 (undergoing neoadjuvant chemoradiation for oncologic reasons). OBJECTIVE: The purpose of this study was to compare patients with local regrowth requiring salvage resection according to their baseline stage. DESIGN: This was a retrospective review of consecutive patients with nonmetastatic distal rectal cancer undergoing neoadjuvant chemoradiation. SETTINGS: The study included 2 independent tertiary centers with institutional watch-and-wait organ preservation programs. PATIENTS: Consecutive patients with distal rectal cancer (cT2-4N1-2M0) managed by watch and wait and local regrowth from 2 institutions were included. MAIN OUTCOMES MEASURES: Final pathologic features and surgical and oncologic outcomes were compared according to baseline staging. RESULTS: A total of 73 of 257 patients experienced local regrowth. cT2 presented similar to ypT, ypN, R0, and abdominal perineal resection rates (p > 0.05) at the time of salvage when compared with cT3 to cT4. Patients with cT2 at baseline were more likely to undergo an organ preservation procedure for salvage (56.2% vs 26.5%; p = 0.03). Overall and disease-free survival after salvage were similar between groups irrespective of the type of surgery for the regrowth. LIMITATIONS: Retrospective study, small sample size, and possible inaccurate baseline staging. CONCLUSIONS: Although patients with baseline cT2 rectal cancer had similar pathologic stage at the time of recurrence, these patients were more likely to continue an organ preservation pathway after local regrowth through transanal local excision when compared with cT3 to cT4. Despite differences in the use of radical salvage resection, there were no differences in oncologic outcomes. See Video Abstract at http://links.lww.com/DCR/B254. CIRUGÍA DE RESCATE CON PRESERVACIÓN DE ORGANO PARA PACIENTES CON RECIDIVA LOCAL LUEGO DE WATCH & WAIT: ¿SIGUE SIENDO POSIBLE?: Los pacientes con cáncer rectal que logran una respuesta clínica completa luego de la quimiorradiación neoadyuvante han sido tratados de forma no quirúrgica. El treinta por ciento de estos pacientes pueden desarrollar un nuevo crecimiento local y generalmente se recomienda la resección de rescate con cirugía radical. Sin embargo, en pacientes seleccionados se podría ofrecer la posibilidad de preservación de órgano mediante escisión local. Se formuló la hipótesis de que los pacientes con estadio clinico inicial T2 y sometidos a terapia neoadyuvante (con el propósito específico de lograr una respuesta clínica completa) tenían más probabilidades de presentar una recurrencia local en una etapa más temprana y suceptibles de estrategias de preservación de órgano (escisión local) en comparación con T3 / T4 (sometidos a nCRT por razones oncológicas).Comparar los pacientes con recidiva local que requirieron cirugia de rescate de acuerdo con su estadio inicial.Revisión retrospectiva de pacientes consecutivos con cáncer de recto distal no metastásico sometidos a quimiorradiación neoadyuvante.Dos centros terciarios independientes con programas institucionales de preservación de órgano - Watch & Wait.Pacientes consecutivos con cáncer rectal distal (cT2-4N1-2M0) manejados por Watch & Wait y recidiva local.Las características patológicas finales, los resultados quirúrgicos y oncológicos se compararon de acuerdo con la estadificación inicial.Un total de 73 de 257 pacientes presentaron recidiva local. cT2 presentaron similares ypT, ypN, R0 y tasas de resección abdominoperineal (p>0,05) en el momento del rescate en comparación con cT3-4.Los pacientes con cT2 de base tuvieron más probabilidades de someterse a un procedimiento de preservación de órgano durante el rescate (56,2% frente a 26,5%; p = 0,03). Supervivencia general y DFS después del rescate fueron similares entre los grupos, independientemente del tipo de cirugía para la recidiva.Estudio retrospectivo, tamaño de muestra pequeño, la posible estadificación basal inexacta.Aunque los pacientes con cáncer rectal cT2 de base presentaron estadio patologico similar en el momento de la recidiva, estos pacientes tuvieron más probabilidades de continuar una vía de preservación de órgano luego de una recidiva local a través de la escisión local transanal en comparación con cT3-4. A pesar de las diferencias en el uso de la resección radical de rescate, no hubo diferencias en los resultados oncológicos. Consulte Video Resumen en http://links.lww.com/DCR/B254.

The split scar sign as an indicator of sustained complete response after neoadjuvant therapy in rectal cancer.

OBJECTIVES: To measure the diagnostic performance of a new radiologic pattern on restaging magnetic resonance (MR) high-resolution T2-weighted imaging (T2-WI)-the split scar sign-for the identification of sustained complete response (SCR) after neoadjuvant therapy in rectal cancer. METHODS: Institutional review board approval was obtained for this retrospective study and the informed consent requirement was waived. Fifty-eight consecutive patients with rectal cancer who underwent neoadjuvant therapy were enrolled. Two radiologists blindly and independently reviewed restaging pelvic MR imaging and recorded the presence/absence of the split scar sign (mrSSS). On a second round, they also assessed the relative proportion of intermediate signal intensity on T2-WI (mrT2) and of high signal intensity on high b-value diffusion-weighted imaging (mrDWI). Endoscopic response grading records were retrieved. Qui-square test was employed in search for associations between SCR, defined as pathologic complete response or long-term recurrence-free clinical follow-up, and mrSSS, mrT2, mrDWI and endoscopy. Interobserver agreement for imaging parameters was estimated using Cohen's kappa (k). RESULTS: mrSSS was significantly associated with SCR, with specificity = 0.97/0.97, sensitivity = 0.52/0.64, PPV = 0.93/0.94, NPV = 0.73/0.78, and AuROC = 0.78/0.83, for observers 1/2, respectively. mrDWI was significantly associated with SCR for observer 2, with specificity = 0.76, sensitivity = 0.60, PPV = 0.65, NPV = 0.71, and AuROC = 0.69. mrT2 and endoscopy were not discriminative. Interobserver agreement was substantial for mrSSS (k = 0.69), moderate for mrDWI (k = 0.46), and poor for mrT2 (k = 0.17). CONCLUSION: The split scar sign is a simple morphologic pattern visible on restaging T2-WI which, although not sensitive, is very specific for the identification of sustained complete responders after neoadjuvant therapy in rectal cancer. KEY POINTS: • The split scar sign is a morphologic pattern visible on high-resolution T2-weighted MR imaging in rectal cancer patients after neoadjuvant therapy. It therefore does not require any changes to standard protocol. • At first restaging pelvic MR imaging (mean: 9.1 weeks after the end of radiotherapy), the split scar sign identified patients who sustained a complete response with very high specificity (0.97) and positive predictive value (0.93-0.94). • The split scar sign has the potential to improve patient selection for "watch-and-wait" after neoadjuvant therapy in rectal cancer.