Cost-effectiveness of Total Neoadjuvant Therapy With Short-Course Radiotherapy for Resectable Locally Advanced Rectal Cancer.

Importance: Short-course radiotherapy and total neoadjuvant therapy (SCRT-TNT) followed by total mesorectal excision (TME) has emerged as a new treatment paradigm for patients with locally advanced rectal adenocarcinoma. However, the economic implication of this treatment strategy has not been compared with that of conventional long-course chemoradiotherapy (LCCRT) followed by TME with adjuvant chemotherapy. Objective: To perform a cost-effectiveness analysis of SCRT-TNT vs LCCRT in conjunction with TME for patients with locally advanced rectal cancer. Design, Setting, and Participants: A decision analytical model with a 5-year time horizon was constructed for patients with biopsy-proven, newly diagnosed, primary locally advanced rectal adenocarcinoma treated with SCRT-TNT or LCCRT. Markov modeling was used to model disease progression and patient survival after treatment in 3-month cycles. Data on probabilities and utilities were extracted from the literature. Costs were evaluated from the Medicare payer's perspective in 2020 US dollars. Sensitivity analyses were performed for key variables. Data were collected from October 3, 2020, to January 20, 2021, and analyzed from November 15, 2020, to April 25, 2021. Exposures: Two treatment strategies, SCRT-TNT vs LCCRT with adjuvant chemotherapy, were compared. Main Outcomes and Measures: Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio and net monetary benefits. Effectiveness was defined as quality-adjusted life-years (QALYs). Both costs and QALYs were discounted at 3% annually. Willingness-to-pay threshold was set at $50 000/QALY. Results: During the 5-year horizon, the total cost was $41 355 and QALYs were 2.21 for SCRT-TNT; for LCCRT, the total cost was $54 827 and QALYs were 2.12, resulting in a negative incremental cost-effectiveness ratio (-$141 256.77). The net monetary benefit was $69 300 for SCRT-TNT and $51 060 for LCCRT. Sensitivity analyses using willingness to pay at $100 000/QALY and $150 000/QALY demonstrated the same conclusion. Conclusions and Relevance: These findings suggest that SCRT-TNT followed by TME incurs lower cost and improved QALYs compared with conventional LCCRT followed by TME and adjuvant chemotherapy. These data offer further rationale to support SCRT-TNT as a novel cost-saving treatment paradigm in the management of locally advanced rectal cancer.

Management Trends and Outcomes of Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder: Evolution of the University of Southern California Experience over 3,347 Cases.

PURPOSE: There are conflicting reports on outcome trends following radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS: Evolution of modern bladder cancer management and its impact on outcomes was analyzed using a longitudinal cohort of 3,347 patients who underwent RC at an academic center between 1971 and 2018. Outcomes included recurrence-free survival (RFS) and overall survival (OS). Associations were assessed using univariable and multivariable models. RESULTS: In all, 70.9% of cases underwent open RC in the last decade, although trend for robot-assisted RC rose since 2009. While lymphadenectomy template remained consistent, nodal submission changed to anatomical packets in 2002 with increase in yield (p <0.001). Neoadjuvant chemotherapy (NAC) use increased with time with concomitant decrease in adjuvant chemotherapy; this was notable in the last decade (p <0.001) and coincided with improved pT0N0M0 rate (p=0.013). Median 5-year RFS and OS probabilities were 65% and 55%, respectively. Advanced stage, NAC, delay to RC, lymphovascular invasion and positive margins were associated with worse RFS (all, multivariable p <0.001). RFS remained stable over time (p=0.73) but OS improved (5-year probability, 1990-1999 51%, 2010-2018 62%; p=0.019). Among patients with extravesical and/or node-positive disease, those who received NAC had worse outcomes than those who directly underwent RC (p ≤0.001). CONCLUSIONS: Despite perioperative and surgical advances, and improved pT0N0M0 rates, there has been no overall change in RFS trend following RC, although OS rates have improved. While patients who are downstaged with NAC derive great benefit, our real-world experience highlights the importance of preemptively identifying NAC nonresponders who may have worse post-RC outcomes.

Initial treatment and survival in Danish patients diagnosed with non-small-cell lung cancer (2005-2015): SCAN-LEAF study.

Aim: To describe initial treatment patterns and survival of patients diagnosed with non-small-cell lung cancer (NSCLC) in Denmark, before immune checkpoint inhibitor and later-generation tyrosine kinase inhibitor use. Patients & methods: Adults diagnosed with incident NSCLC (2005-2015; follow-up: 2016). Initial treatments and overall survival (OS) are reported. Results: 31,939 NSCLC patients (51.6% stage IV) were included. Increasing use of curative radiotherapy/chemoradiation for stage I, II/IIIA and IIIB NSCLC coincided with improved 2-year OS. Systemic anticancer therapy use increased for patients with stage IV non-squamous NSCLC (53.0-60.6%) but not squamous NSCLC (44.9-47.3%). 1-year OS improved in patients with stage IV non-squamous NSCLC (23-31%) but not squamous NSCLC (22-25%). Conclusion: Trends indicated improved OS as treatments evolved between 2005 and 2015, but the effect was limited to 1-year OS in stage IV disease.

Outcomes of Patients With Local Regrowth After Nonoperative Management of Rectal Cancer After Neoadjuvant Chemoradiotherapy.

BACKGROUND: Clinical complete responders after chemoradiation for rectal cancer are increasingly being managed by a watch-and-wait strategy. Nonetheless, a significant proportion will experience a local regrowth, and the long-term oncological outcomes of these patients is not totally known. OBJECTIVE: The purpose of this study was to analyze the outcomes of patients who submitted to a watch-and-wait strategy and developed a local regrowth, and to compare these results with sustained complete clinical responders. DESIGN: This was a retrospective study. SETTING: Single institution, tertiary cancer center involved in alternatives to organ preservation. PATIENTS: Patients with a biopsy-proven rectal adenocarcinoma (stage II/III or low lying cT2N0M0 at risk for an abdominoperineal resection) treated with chemoradiation who were found at restage to have a clinical complete response. INTERVENTIONS: Rectal cancer patients treated with chemoradiation who underwent a watch-and-wait strategy (without a full thickness local excision) and developed a local regrowth were compared to the remaining patients of the watch-and-wait strategy. MAIN OUTCOME MEASURES: Overall survival between groups, incidence of regrowth' and results of salvage surgery. RESULTS: There were 67 patients. Local regrowth occurred in 20 (29.9%) patients treated with a watch-and-wait strategy. Mean follow-up was 62.7 months. Regrowth occurred at mean 14.2 months after chemoradiation, half of them within the first 12 months. Patients presented with comparable initial staging, lateral pelvic lymph-node metastasis, and extramural venous invasion. The regrowth group had a statistically nonsignificant higher incidence of mesorectal fascia involvement (35.0% vs 13.3%, p = 0.089). All regrowths underwent salvage surgery, mostly (75%) a sphincter-sparing procedure. 5-year overall survival was 71.1% in patients with regrowth and 91.1% in patients with a sustained complete clinical response (p = 0.027). LIMITATIONS: This study was limited by its retrospective evaluation of patient selection for a watch-and-wait strategy and outcomes, as well as its small sample size. CONCLUSIONS: Local regrowth is a frequent event when following a watch-and-wait policy (29.9%); however, patients could undergo salvage surgical treatment with adequate pelvic control. In this series, overall survival showed a statistically significant difference from patients managed with a watch-and-wait strategy who experienced a local regrowth compared to those who did not. See Video Abstract at http://links.lww.com/DCR/B773.RESULTADOS DE LOS PACIENTES CON REBROTE LOCAL, DESPUÉS DEL MANEJO NO QUIRÚRGICO DEL CÁNCER DE RECTO, DESPUÉS DE LA QUIMIORRADIOTERAPIA NEOADYUVANTEANTECEDENTES:Los respondedores clínicos completos, después de la quimiorradiación para el cáncer de recto, se tratan cada vez más mediante una estrategia de observación y espera. No obstante, una proporción significativa experimentará un rebrote local y los resultados oncológicos a largo plazo de estos pacientes, no se conocen por completo.OBJETIVO:El propósito de este estudio, fue analizar los resultados de los pacientes sometidos a una estrategia de observación y espera, que desarrollaron un rebrote local, y comparar estos resultados con respondedores clínicos completos sostenidos.DISEÑO:Este fue un estudio retrospectivo.ENTORNO CLINICO.Institución única, centro oncológico terciario involucrado en alternativas a la preservación de órganos.PACIENTES:Pacientes con un adenocarcinoma de recto comprobado por biopsia (estadio II / III o posición baja cT2N0M0, en riesgo de resección abdominoperineal), tratados con quimiorradiación, y que durante un reestadiaje, presentaron una respuesta clínica completa.INTERVENCIONES:Los pacientes con cáncer de recto tratados con quimiorradiación, sometidos a una estrategia de observación y espera (sin una escisión local de espesor total) y que desarrollaron un rebrote local, se compararon con los pacientes restantes de la estrategia de observación y espera.PRINCIPALES MEDIDAS DE VALORACION:Supervivencia global entre los grupos, incidencia de rebrote y resultados de la cirugía de rescate.RESULTADOS:Fueron 67 pacientes. El rebrote local ocurrió en 20 (29,9%) pacientes tratados con una estrategia de observación y espera. El seguimiento medio fue de 62,7 meses. El rebrote se produjo a la media de 14,2 meses después de la quimiorradiación, la mitad de ellos dentro de los primeros 12 meses. Los pacientes se presentaron con una estadificación inicial comparable, metástasis en los ganglios linfáticos pélvicos laterales e invasión venosa extramural. El grupo de rebrote tuvo una mayor incidencia estadísticamente no significativa de afectación de la fascia mesorrectal (35,0 vs 13,3%, p = 0,089). Todos los rebrotes se sometieron a cirugía de rescate, en su mayoría (75%) con procedimiento de preservación del esfínter. La supervivencia global a 5 años fue del 71,1% en pacientes con rebrote y del 91,1% en pacientes con una respuesta clínica completa sostenida (p = 0,027).LIMITACIONES:Evaluación retrospectiva de la selección de pacientes para una estrategia y resultados de observar y esperar, tamaño de muestra pequeño.CONCLUSIONES:El rebrote local es un evento frecuente después de la política de observación y espera (29,9%), sin embargo los pacientes podrían someterse a un tratamiento quirúrgico de rescate con un adecuado control pélvico. En esta serie, la supervivencia global mostró una diferencia estadísticamente significativa de los pacientes manejados con una estrategia de observación y espera que experimentaron un rebrote local, en comparación con los que no lo hicieron. Consulte Video Resumen en http://links.lww.com/DCR/B773. (Traducción-Dr. Fidel Ruiz Healy).

Association Between Surgical Volume and Survival Among Patients With Variant Histologies of Bladder Cancer.

OBJECTIVE: To examine the relationship between hospital volume and the management of bladder cancer variant histology. Variant histologies of bladder cancer are rare which limits the ability for providers to develop expertise however there is a clear hospital and/or surgeon-volume relationship for management of rare or complex surgical and/or medical diseases. METHODS: We queried the National Cancer Database from 2004-2016 for all cases of bladder cancer, identifying cases of variant histology. Our primary outcome was overall survival while secondary outcomes included identifying treatment patterns. Hospitals were stratified into those that managed ≤2, >2-4, >4-6, and ≥6 cases per year of variant histology. RESULTS: We identified 23,284 patients with bladder cancer of variant histology who were treated at 1301 hospitals. Few institutions had high volume experience with this disease: 18.5% (n = 241) treated >2 patients annually and 5.7% (n = 76) treated >4 cases annually. Hospital volume positively correlated with utilization of early radical cystectomy (RC) in non-muscle invasive disease and neoadjuvant chemotherapy in muscle-invasive disease. On multivariable analysis, increased hospital volume was associated with improved survival. After stratifying by sub-type, hospital volume continued to be associated with improved survival for squamous, small cell, and sarcomatoid cancers. CONCLUSION: Management of variant histology urothelial carcinoma at high-volume centers is associated with improved overall survival. The mechanisms of this are multifactorial, and future research should focus on improvement opportunities for low-volume hospitals, centralization of care, and/or increased access to care at high-volume centers.

Feasibility Study of Transanal Irrigation Using a Colostomy Irrigation System in Patients With Low Anterior Resection Syndrome.

BACKGROUND: Low anterior resection syndrome has a negative impact on quality of life. Intestinal irrigation is a method of lavage consisting of a scheduled evacuation. OBJECTIVE: This study aims to evaluate functional and quality-of-life outcomes in patients with low anterior resection syndrome after transanal irrigation using a colostomy irrigation system. DESIGN: This was a prospective case series. SETTINGS: This study presents a single-center experience at a tertiary oncological center in an upper-middle-income country. PATIENTS: Patients classified as having minor or major low anterior resection syndrome 12 months after their operation were selected. INTERVENTIONS: Transanal irrigation was performed using an ostomy irrigation kit. Questionnaires assessing patients' bowel function (low anterior resection syndrome and Wexner score) and quality of life (Short Form-36 questionnaire) were applied before and after treatment. MAIN OUTCOME MEASURES: The primary outcomes were low anterior resection syndrome score and quality-of-life improvement after a 12-month treatment. RESULTS: Of the 22 patients included, 20 had major and 2 had minor low anterior resection syndrome, with a median score of 39, especially high rates of incontinence for liquid stool (21; 95.5%), clustering (21; 95.5%), and urgency (17; 77.3%). All patients successfully completed the 3-day training, and there were no complications during the treatment. After the 12-month period, the median score was 8, with 90% of the patients classified as having "no syndrome" and great improvement in all domains of this score. The most improved quality-of-life sections were patient vitality (p = 0.025) and physical (p = 0.002), social (p = 0.001), and emotional aspects (p = 0.001). LIMITATIONS: The study was limited by its small sample size and the limited follow-up period. CONCLUSIONS: This study presents a safe implementation protocol of an ostomy irrigation device for transanal irrigation. It also adds to the literature that transanal irrigation is a safe, effective, and easily implemented procedure for patients with low anterior resection syndrome with a significant improvement in quality of life. See Video Abstract at http://links.lww.com/DCR/B563.ESTUDIO DE FACTIBILIDAD DE LA IRRIGACIÓN TRANSANAL UTILIZANDO EL SISTEMA DE IRRIGACIÓN PARA COLOSTOMÍA EN PACIENTES CON SÍNDROME DE RESECCIÓN ANTERIOR BAJAANTECEDENTES:El síndrome de resección anterior baja tiene un impacto negativo en la calidad de vida de los pacientes. La irrigación intestinal es un método de lavado que consiste en evacuaciones programadas.OBJETIVOS:Evaluar los resultados de la funcionalidad e impacto en la calidad de vida de los pacientes con síndrome de resección anterior y baja posterior a la irrigación transanal utilizando un sistema de irrigación de colostomía.DISEÑO:Es estudio prospectivo de una serie de casos.ESCENARIO:En este estudio se muestra la experiencia de un centro oncológico de tercer nivel en un país en vías de desarrollo.PACIENTES:Aquellos clasificados como síndrome con afección en menor o mayor grado doce meses después de la cirugía.METODO:Se efectuó irrigación transanal utilizando un equipo de irrigación de estomas. Se aplicaron cuestionarios para valorar la función intestinal de los pacientes (síndrome de resección anterior baja y la escala de Wexner) y para calidad de vida (Cuestionario Corto-36) antes y después del tratamiento.EVALUACION DE LOS RESULTADOS PRINCIPALES:Los principales resultados se obtuvieron de la escala del síndrome de resección baja y la mejoría en la calidad vida doce meses después de tratamiento.RESULTADOS:De los veintidós pacientes incluidos, veinte presentaron manifestaciones mayores del síndrome de resección baja y dos, manifestaciones menores. Con una media de treinta y nueve, se encontraron, especialmente, altos índices de incontinencia a líquidos (21; 95'5%) hiperdefecación "clustering" (21; 95'5%) y urgencia (17; 77'3%). Todos los pacientes completaron en forma satisfactoria el entrenamiento de tres días sin presentarse complicaciones durante el tratamiento. Al término del mes doce la media fue de ocho, con el 90% de los pacientes clasificados como "sin síndrome" y se observó una mejoría substancial en todos los puntos de la evaluación. Las secciones de calidad de vida que mostraron una mejoría significativa fueron: la vitalidad del paciente (p = 0'025), física (p = 0'002), social (p = 0'001) y emocional (p = 0'001).LIMITACIONES:El tamaño de la muestra es pequeño y el tiempo de seguimiento corto.CONCLUSIONES:Este estudio muestra la implementación de un protocolo seguro para la irrigación de estomas mediante un dispositivo transanal. Además contribuye con el concepto en la literatura de que la seguridad de la irrigación transanal es seguro, efectivo y facilmente reproducible para pacientes con síndrome de resección anterior baja con una mejoría significativa en la calidad de vida. Consulte Video Resumen en http://links.lww.com/DCR/B563. (Traducción-Dr. Miguel Esquivel-Herrera).

Four versus 3 Cycles of Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Implications for Pathological Response and Survival.

PURPOSE: The ideal number of neoadjuvant chemotherapy (NAC) cycles for muscle-invasive bladder cancer is uncertain with 3 to 4 representing the standard of care (SOC). We compared ypT0 rates and survival between patients receiving 4 versus 3 cycles of NAC with evaluation of chemotherapy-related toxicity for correlation with tumor chemosensitivity and pathological response. MATERIALS AND METHODS: Patients receiving NAC followed by radical cystectomy for cT2-4N0M0 urothelial carcinoma from 2 institutions were included. Primary study groups included 4 cisplatin-based NAC cycles, 3 cisplatin-based NAC cycles, and nonSOC NAC (1-2 cycles or noncisplatin-based) to compare ypT0/≤ypT1 rates and survival. A cohort of patients not receiving NAC was included for pathological reference. RESULTS: Of 693 total patients, 318 (45.9%) received NAC. ypT0 and ≤ypT1 rates were 42/157 (26.8%) and 86/157 (54.8%) for 4 cycles, 38/114 (33.3%) and 71/114 (62.3%) for 3 cycles, and 6/47 (12.8%) and 13/47 (27.7%) for nonSOC (p=0.03 and p <0.01, respectively). Pathological response appeared higher among patients receiving 3 cycles due to toxicity (ypT0: 29/77 [37.7%]; ≤ypT1: 51/77 [66.2%]) but did not reach statistical significance. Toxicities leading to treatment modifications were thrombocytopenia (32.1%), neutropenia (27.2%), renal insufficiency (22.2%), and constitutional symptoms (18.5%). NonSOC patients had lower Kaplan-Meier survival (cT2-cT4N0M0: log-rank p=0.07; cT2N0M0: log-rank p=0.02). There were no statistically significant differences in survival between 4 and 3 cycles (HR 1.00 [95% CI 0.57-1.74], p=0.99). CONCLUSIONS: Patients completing 3 cycles of cisplatin-based NAC have similar pathologic response and short-term survival compared to 4 cycles. Further evaluation of patients experiencing toxicity as a potential marker of tumor chemosensitivity is needed.

Identifying the Optimal Number of Neoadjuvant Chemotherapy Cycles in Patients with Muscle Invasive Bladder Cancer.

PURPOSE: We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer. MATERIALS AND METHODS: In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated. RESULTS: pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08). CONCLUSIONS: Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.

MINImal vs. MAXimal Invasive Axillary Staging and Treatment After Neoadjuvant Systemic Therapy in Node Positive Breast Cancer: Protocol of a Dutch Multicenter Registry Study (MINIMAX).

BACKGROUND: Node positive breast cancer (cN+) patients with an axillary pathologic complete response after neoadjuvant systemic therapy (NST) are not expected to benefit from axillary lymph node dissection (ALND). Therefore, less invasive axillary staging procedures have been introduced to establish response-guided treatment. However, evidence is lacking with regard to their oncologic safety and impact on quality of life (QoL). We hypothesize that if response-guided treatment is given, less invasive staging procedures are non-inferior to standard ALND in terms of oncologic safety, and superior to standard ALND in terms of QoL. PATIENTS AND METHODS: MINIMAX is a Dutch multicenter registry study that includes patients with cN1-3M0 unilateral invasive breast cancer, who receive NST, followed by axillary staging and treatment according to local protocols. In a retrospective registry of ±4000 patients, the primary endpoint is oncologic safety at 5 and 10 years (disease-free, breast-cancer-specific and overall survival, and axillary recurrence rate). In a prospective multicenter registry, the primary endpoints are QoL at 1 and 5 years, and we aim to verify the 5-year oncologic safety. With an estimated 5-year disease-free survival of 72.5% and anticipated loss to follow-up of 10%, a sample size of 549 is needed to have 80% power to detect non-inferiority (with a 10% margin) of less invasive staging procedures. CONCLUSION: In cN+ patients treated with NST, less invasive axillary staging procedures are already implemented globally. Evidence is needed to support the assumed oncologic safety and superior QoL of such procedures. This study will contribute to evidence-based guidelines.

System-Level Determinants of Access to Flap Reconstruction after Abdominoperineal Resection.

BACKGROUND: Reconstruction following abdominoperineal resection improves outcomes by reducing wound-related complications, particularly in irradiated patients. Little is known regarding system-level factors that impact patients' access to reconstructive surgery following abdominoperineal resection. This study aimed to identify barriers to undergoing reconstruction following abdominoperineal resection. METHODS: Using the National Inpatient Sample database from 2012 to 2014, all encounters with colorectal or anorectal carcinoma patients who underwent abdominoperineal resection were extracted based on International Classification of Disease, Ninth Revision, diagnosis and procedure codes. Multivariable logistic regression analyzed the outcome of undergoing reconstruction. RESULTS: The weighted sample included encounters with 19,205 abdominoperineal resection patients, of whom 1243 (6.5 percent) received a flap. Notable patient-level predictors of receiving a flap included age younger than 55 years (OR, 1.82; 95 percent CI, 1.23 to 2.74; p = 0.003) and neoadjuvant chemoradiation therapy (OR, 1.37; 95 percent CI, 1.01 to 1.88; p = 0.041). Race, sex, income level, insurance type, and Elixhauser Comorbidity Index were not associated with increased odds of receiving a flap. For facility-level factors, urban teaching hospitals (OR, 23.6; 95 percent CI, 3.29 to 169.4; p = 0.002) and larger hospital bedsize (OR, 2.64; 95 percent CI, 1.53 to 4.56; p = 0.000) were associated with higher odds of reconstruction. Plastic surgery facility volume was not found to be a significant predictor of undergoing flap reconstruction (p > 0.05). CONCLUSIONS: Patients undergoing abdominoperineal resection at academic centers were over 23 times more likely to undergo reconstruction, after adjusting for available confounders. Patients undergoing abdominoperineal resection at smaller, nonacademic centers may not have equitable access to reconstruction despite being appropriate candidates. Given the morbidity of abdominoperineal resection, patients should be referred to large, academic centers to have access to flap reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Identification of DNA methylation biomarkers with potential to predict response to neoadjuvant chemotherapy in triple-negative breast cancer.

Neoadjuvant chemotherapy (NAC) is used to treat triple-negative breast cancer (TNBC) prior to resection. Biomarkers that accurately predict a patient's response to NAC are needed to individualise therapy and avoid chemotoxicity from unnecessary chemotherapy. We performed whole-genome DNA methylation profiling on diagnostic TNBC biopsy samples from the Sequential Evaluation of Tumours Undergoing Preoperative (SETUP) NAC study. We found 9 significantly differentially methylated regions (DMRs) at diagnosis which were associated with response to NAC. We show that 4 of these DMRs are associated with TNBC overall survival (P < 0.05). Our results highlight the potential of DNA methylation biomarkers for predicting NAC response in TNBC.

Spatial and temporal intratumour heterogeneity has potential consequences for single biopsy-based neuroblastoma treatment decisions.

Intratumour heterogeneity is a major cause of treatment failure in cancer. We present in-depth analyses combining transcriptomic and genomic profiling with ultra-deep targeted sequencing of multiregional biopsies in 10 patients with neuroblastoma, a devastating childhood tumour. We observe high spatial and temporal heterogeneity in somatic mutations and somatic copy-number alterations which are reflected on the transcriptomic level. Mutations in some druggable target genes including ALK and FGFR1 are heterogeneous at diagnosis and/or relapse, raising the issue whether current target prioritization and molecular risk stratification procedures in single biopsies are sufficiently reliable for therapy decisions. The genetic heterogeneity in gene mutations and chromosome aberrations observed in deep analyses from patient courses suggest clonal evolution before treatment and under treatment pressure, and support early emergence of metastatic clones and ongoing chromosomal instability during disease evolution. We report continuous clonal evolution on mutational and copy number levels in neuroblastoma, and detail its implications for therapy selection, risk stratification and therapy resistance.

Analysis of Adjuvant Chemotherapy on Pathological Remission of Breast Cancer.

With the continuous development of the concept of diagnosis and treatment, the current industry's treatment model has developed into a multidisciplinary comprehensive treatment. That is, in view of the pathological characteristics and clinical stages of breast cancer, corresponding methods such as surgery, chemotherapy, endocrine therapy, radiotherapy, and biological targeted therapy are adopted to provide comprehensive treatment of patients with multiple disciplines. This paper combines experimental research to research and analyze the degree of pathological remission of breast cancer by adjuvant chemotherapy and combines investigation and analysis and group trials to study and explore the effect of adjuvant chemotherapy. Moreover, this paper fully considers the patient's response to neoadjuvant chemotherapy and compares the changes in tumor cell abundance before and after chemotherapy to observe the response of the patient's primary tumor to chemotherapy at a microscopic level. Therefore, this study has made a relatively objective and accurate evaluation of the chemotherapy efficacy of tumor tissues, which can provide a reference for subsequent related research.

[Rectal Cancer: Organ preservation and neoadjuvant treatment escalation]. / Cancer du rectum : préservation d'organe et escalade du traitement néo-adjuvant.

Standard treatment consisting of chemoradiotherapy followed by radical surgery with total mesorectal excision, results in good oncologic local control but high morbidity and poor functional results. Since chemoradiotherapy results in 15% pathological complete response, even reaching up to 30% in case of association with neoadjuvant chemotherapy, radical surgery has been recently debated for good responders. Therefore, a de-escalation strategy, by omitting radical surgery in good responders, has recently been developed with two different options: a watch and wait strategy, requiring an accurate clinical and radiological definition of complete response and a local excision strategy including patients with sub-complete response. Ongoing trials focus on response optimization by chemotherapy intensification or radiotherapy dose escalation. However, many questions are still to be answered regarding definition of complete response, follow-up strategy, morbidity of salvage surgery in case of recurrence as well as long-term oncological and functionnal results.

Understanding Preoperative Breast Satisfaction among Patients Undergoing Mastectomy and Immediate Reconstruction: BREAST-Q Insights.

BACKGROUND: This study aims to present normative values for satisfaction with breasts among preoperative breast reconstruction patients as assessed using the BREAST-Q instrument and to delineate factors associated with preoperative breast satisfaction. METHODS: A retrospective analysis of prospectively collected data was performed examining women undergoing postmastectomy breast reconstruction at a tertiary care center who preoperatively completed the BREAST-Q from 2010 to 2017. Because breast satisfaction scores were nonnormally distributed, scores were categorized into quartiles for analysis. Patient- and treatment-level variables were tested in a multivariable ordinal logistic regression model as predictors of breast satisfaction. Preoperative satisfaction was also tested for association with choice of reconstructive modality. RESULTS: Among 1306 postmastectomy reconstruction patients included in the study, mean preoperative Satisfaction with Breasts score was 61.8 ± 21.5 and the median score was 58.0 (interquartile range, 48 to 70). Factors associated with significantly lower preoperative satisfaction included history of psychiatric diagnosis, preoperative radiotherapy, marital status (married), and higher body mass index. Factors associated with significantly higher scores were malignancy (localized tumor), medium bra size (B to C cup), and self-identification as black. Preoperative breast satisfaction was lower among patients who elected autologous reconstruction than among those with implant reconstruction (p < 0.001). CONCLUSIONS: Preoperative breast satisfaction is influenced by multiple factors. Understanding these factors may improve preoperative counseling and expectation management for patients who undergo postmastectomy breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Patterns and timing of recurrence in esophageal squamous cell carcinoma patients treated with neoadjuvant chemoradiotherapy plus esophagectomy.

BACKGROUND: Tumor regression grade (TRG) after neoadjuvant therapy is reportedly predictive of prognosis in esophageal cancer patients, as lack of a response to neoadjuvant therapy is associated with a poor prognosis. However, there is little information available on the timing and pattern of recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma (TESCC) that takes into consideration TRG after neoadjuvant chemoradiotherapy (NACRT). Here, in an effort to gain insight into a treatment strategy that improves the prognosis of NACRT non-responders, we evaluated the patterns and timing of recurrence in TESCC patients, taking into consideration TRG after NACRT. METHODS: A total of 127 TESCC patients treated with NACRT and esophagectomy between 2009 and 2017 were enrolled in this observational cohort study. TRGs were assigned based on the proportion of residual tumor cells in the area (TRG1, ≥1/3 viable cancer cells; 2, < 1/3 viable cancer cells; 3, no viable cancer cells). We retrospectively investigated the timing and patterns of recurrence and the prognoses in TESCC patients, taking into consideration TRG after NACRT. RESULTS: The 127 participating TESCC patients were categorized as TRG1 (42 patients, 33%), TRG2 (56 patients, 44%) or TRG3 (29 patients, 23%). The locoregional recurrence rate was higher in TRG1 (36.4%) patients than combined TRG2-3 (7.4%) patients. Patients with TRG3 had better prognoses, though a few TRG3 patients experienced distant recurrence. There were no significant differences in median time to first recurrence or OS among patients with locoregional or distant recurrence. There was a trend toward better OS in TRG2-3 patients with recurrence than TRG1 patients with recurrence, but the difference was not significant. CONCLUSIONS: NACRT non-responders (TRG1 patients) experienced higher locoregional recurrence rates and earlier recurrence with distant or locoregional metastasis. TRG appears to be useful for establishing a strategy for perioperative treatments to improve TESCC patient survival, especially among TRG1 patients. (303 words).

Impact of COVID-19 Pandemic on Surgical Breast Cancer Patients Undergoing Neoadjuvant Therapy: A Multicentric Study.

BACKGROUND/AIM: Due to the SARS-CoV-2 pandemic, many scientific committees proposed neoadjuvant therapy (NACT) bridging treatment as a novel strategy and indication. The aim of the study was to evaluate the impact of COVID-19 pandemic on breast cancer patients undergoing NACT. PATIENTS AND METHODS: All breast cancer patients referred to two Breast Units during COVID-19-pandemic were enrolled. RESULTS: Out of 814 patients, 43(5.3%) were enrolled in the COVID-19-group and compared with 94 (7.9%) similar Pre-COVID-19 patients. We observed a reduction in the number of patients undergoing NACT, p=0.0019. No difference was reported in terms of clinical presentation, indications, and tumor response. In contrast, a higher number of vascular adverse events was reported (6.9% vs. 0% p=0.029). Immediate breast cancer reconstructions following invasive surgery suffered a significant slowdown (5.9% vs. 47.7%, p=0.019). CONCLUSION: COVID-19 caused a reduction in the number of patients undergoing NACT, with no changes in terms of indications, clinical presentation, and tumor response. Furthermore, there was an increased incidence of vascular events.

Diffusion-weighted MRI for predicting treatment response in patients with nasopharyngeal carcinoma: a systematic review and meta-analysis.

Early prediction of treatment response in nasopharyngeal carcinoma is clinically relevant for optimizing treatment strategies. This meta-analysis was performed to evaluate whether apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) can predict treatment response of patients with nasopharyngeal carcinoma. A systematic search of PubMed-MEDLINE and Embase was performed to identify relevant original articles until July 22, 2021. We included studies which performed DWI for predicting locoregional treatment response in nasopharyngeal carcinoma treated with neoadjuvant chemotherapy, definitive chemoradiation, or radiation therapy. Hazard ratios were meta-analytically pooled using a random-effects model for the pooled estimates of overall survival, local relapse-free survival, distant metastasis-free survival and their 95% CIs. ADC showed a pooled sensitivity of 87% (95% CI 72-94%) and specificity of 70% (95% CI 56-80%) for predicting treatment response. Significant between-study heterogeneity was observed for both pooled sensitivity (I2 = 68.5%) and specificity (I2 = 92.2%) (P < 0.01). The pooled hazard ratios of low pretreatment ADC for assessing overall survival, local relapse-free survival, and distant metastasis-free survival were 1.42 (95% CI 1.09-1.85), 2.31 (95% CI 1.42-3.74), and 1.35 (95% CI 1.05-1.74), respectively. In patients with nasopharyngeal carcinoma, pretreatment ADC demonstrated good predictive performance for treatment response.