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PURPOSE: To systematically review and meta-analyze the prognostic significance of lateral lymph node metastasis (LLNM) on pretreatment MRI in patients with rectal cancer who undergo neoadjuvant chemoradiation followed by curative surgical resection without lateral lymph node dissection (LLND). METHODS: We searched the MEDLINE and EMBASE databases until September 27, 2023, utilizing the following search terms: (rectal OR rectum OR colorectal) AND (lateral OR sidewall) AND (lymph OR node). The QUIPS tool was employed to evaluate methodological quality. We pooled the association between LLNM on pretreatment MRI and outcomes such as local recurrence, distant metastasis, disease-free survival, and overall survival using hazard ratio (HR) and odds ratio (OR) based on random effects model. RESULTS: We included 9 studies, encompassing 3180 patients. LLNM on pretreatment MRI revealed a significant association with increased local recurrence rates (HR: 4.11; 95 % CI: [1.87, 9.02]) and elevated risks for both disease-free (HR: 1.70; 95 % CI: [1.42, 2.03]) and overall survival (HR: 1.76; 95 % CI: [1.44, 2.15]). As for distant metastasis, our analysis indicated a potential trend towards increased rates, though this did not reach statistical significance (HR: 1.67; 95 % CI: [0.85, 3.27]). CONCLUSIONS: Our findings underscore the relationship between LLNM and increased local recurrence and compromised disease-free and overall survival. This emphasizes the potential limitations of relying solely on neoadjuvant chemoradiation and highlights the potential need to intensify treatment in select patients.
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Metástasis Linfática , Imagen por Resonancia Magnética , Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Quimioradioterapia/métodos , Escisión del Ganglio Linfático , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/prevención & control , Pronóstico , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/diagnóstico por imagenRESUMEN
Background: In mucinous rectal cancer, it can be difficult to differentiate between cellular and acellular mucin. The purpose of this study was to evaluate, in patients with mucinous rectal cancer, the value of static enhancement (enh) and pharmacokinetic parameters of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in predicting pathologic complete response. Methods: This retrospective cross-sectional study performed at Memorial Sloan Kettering Cancer Center included 43 patients (24 males and 19 females; mean age, 57 years) with mucinous rectal cancer who underwent MRI at baseline as well as after neoadjuvant chemoradiotherapy but before surgical resection between 2008 and 2019. Two radiologists independently segmented tumors on contrast-enhanced axial 3D T1-weighted images and sagittal DCE magnetic resonance images. On contrast-enhanced axial T1-weighted images, the static parameters enh and relative enhancement (renh) were estimated. On DCE images, the pharmacokinetic parameters Ktrans, kep, relative Ktrans (rKtrans), and relative kep (rkep) were estimated. Associations between all parameters with pathologic complete response were tested using Wilcoxon signed-rank tests. Receiver operating characteristic (ROC) analysis was performed to assess the area under the curve (AUC) for each parameter. Results: Of the 43 patients who were included in the study, 42/43 (98%) had evaluable contrast-enhanced axial T1-weighted images and 35/43 (81%) had evaluable DCE images. Of the patients with evaluable contrast-enhanced axial T1-weighted images, 9/42 (21%) had pathologic complete response and 33/42 (79%) did not have pathologic complete response. For reader 1, enh(pre-neoadjuvant chemotherapy), enh(post-neoadjuvant chemotherapy), and renh were significant predictors of pathologic complete response [P=0.045 (AUC =0.73), 0.039 (AUC =0.74), and 0.0042, respectively]. For reader 2, enh(pre-neoadjuvant chemotherapy) and renh were significant predictors [P=0.021 (AUC =0.77) and 0.002, respectively]. For renh, the AUC was 0.83 for reader 1, and 0.82 for reader 2. Meanwhile, of those patients with evaluable DCE images, 9/35 (26%) had pathologic complete response and 26/35 (74%) did not have pathologic complete response. Ktrans(pre-neoadjuvant chemotherapy), kep(pre-neoadjuvant chemotherapy), and rkep were significant predictors [P=0.016 (AUC =0.73), 0.00057 (AUC =0.81), and 0.0096 (AUC =0.74), respectively]. Conclusions: Static and pharmacokinetic parameters of contrast-enhanced MRI show promise to predict neoadjuvant treatment response. Static enh parameters, which are simpler to assess, showed the strongest prediction.
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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.
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BACKGROUND: A variety of definitions for a clinical near-complete response after neoadjuvant (chemo) radiotherapy for rectal cancer are currently used. This variety leads to inconsistency in clinical practice, long-term outcome, and trial enrollment. OBJECTIVE: The aim of this study was to reach expert-based consensus on the definition of a clinical near-complete response after (chemo) radiotherapy. DESIGN: A modified Delphi process, including a systematic review, 3 surveys, and 2 meetings, was performed with an international expert panel consisting of 7 surgeons and 4 radiologists. The surveys consisted of individual features, statements, and feature combinations (endoscopy, T2-weighted MRI, and diffusion-weighted MRI). SETTING: The modified Delphi process was performed in an online setting; all 3 surveys were completed online by the expert panel, and both meetings were hosted online. MAIN OUTCOME MEASURES: The main outcome was to reach consensus (80% or more agreement). RESULTS: The expert panel reached consensus on a 3-tier categorization of the near-complete response category based on the likelihood of the response to evolve into a clinical complete response after a longer waiting interval. The panelists agreed that a near-complete response is a temporary entity only to be used in the first 6 months after (chemo)radiotherapy. Furthermore, consensus was reached that the lymph node status should be considered when deciding on a near-complete response and that biopsies are not always needed when a near-complete response is found. No consensus was reached on whether primary staging characteristics have to be taken into account when deciding on a near-complete response. LIMITATIONS: This 3-tier subcategorization is expert-based; therefore, there is no supporting evidence for this subcategorization. Also, it is unclear whether this subcategorization can be generalized into clinical practice. CONCLUSIONS: Consensus was reached on the use of a 3-tier categorization of a near-complete response, which can be helpful in daily practice as guidance for treatment and to inform patients with a near-complete response on the likelihood of successful organ preservation. See Video Abstract. UN CONSENSO INTERNACIONAL BASADO EN EXPERTOS ACERCA DE LA DEFINICIN DE UNA RESPUESTA CLNICA CASI COMPLETA DESPUS DE QUIMIORADIOTERAPIA NEOADYUVANTE CONTRA EL CNCER DE RECTO: ANTECEDENTES:Actualmente, se utilizan una variedad de definiciones para una respuesta clínica casi completa después de quimioradioterapia neoadyuvante contra el cáncer de recto. Esta variedad resulta en inconsistencia en la práctica clínica, los resultados a largo plazo y la inscripción en ensayos.OBJETIVO:El objetivo de este estudio fue llegar a un consenso de expertos sobre la definición de una respuesta clínica casi completa después de quimioradioterapia.DISEÑO:Se realizó un proceso Delphi modificado que incluyó una revisión sistemática, 3 encuestas y 2 reuniones con un panel internacional de expertos compuesto por siete cirujanos y 4 radiólogos. Las encuestas consistieron en características individuales, declaraciones y combinaciones de características (endoscopía, T2W-MRI y DWI).AJUSTE:El proceso Delphi modificado se realizó en un entorno en línea; el panel de expertos completó las tres encuestas en línea y ambas reuniones se realizaron en línea.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue llegar a un consenso (≥80% de acuerdo).RESULTADOS:El panel de expertos llegó a un consenso sobre una categorización de tres niveles de la categoría de respuesta casi completa basada en la probabilidad de que la respuesta evolucione hacia una respuesta clínica completa después de un intervalo de espera más largo. Los panelistas coincidieron en que una respuesta casi completa es una entidad temporal que sólo debe utilizarse en los primeros 6 meses después de la quimioradioterapia. Además, se llegó a un consenso en que se debe considerar el estado de los nódulos linfáticos al decidir sobre una respuesta casi completa y que no siempre se necesitan biopsias cuando se encuentra una respuesta casi completa. No se llegó a un consenso sobre si se deben tener en cuenta las características primarias de estadificación al decidir una respuesta casi completa.LIMITACIONES:Esta subcategorización de 3 niveles está basada en expertos; por lo tanto, no hay evidencia que respalde esta subcategorización. Además, no está claro si esta subcategorización puede generalizarse a la práctica clínica.CONCLUSIONES:Se alcanzó consenso sobre el uso de una categorización de 3 niveles de una respuesta casi completa que puede ser útil en la práctica diaria como guía para el tratamiento y para informar a los pacientes con una respuesta casi completa sobre la probabilidad de una preservación exitosa del órgano. (Traducción - Dr. Aurian Garcia Gonzalez).
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Consenso , Técnica Delphi , Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/radioterapia , Terapia Neoadyuvante/métodos , Quimioradioterapia/métodos , Resultado del Tratamiento , Imagen de Difusión por Resonancia Magnética/métodosRESUMEN
OBJECTIVE: Assess the significance of enlarged lateral lymph nodes (LLN) for disease recurrence, metastasis, and organ preservation in patients with rectal cancer. BACKGROUND: Optimal treatment of rectal adenocarcinoma involving LLN is subject to debate. METHODS: A post hoc analysis of the OPRA trial, a multicenter study of patients with rectal cancer treated with total neoadjuvant therapy (TNT) followed by total mesorectal excision or watch-and-wait management. We analyzed the association of visible LLN (LLN+), LLN≥7 mm (short axis) on baseline MRI, and LLN≥4 mm on restaging MRI with recurrence, metastasis, and rectum preservation. RESULTS: At baseline, 57 out of 324 (18%) patients had LLN+. In 30 (53%) of 57 patients with LLN+ on baseline MRI, the LLN disappeared after TNT. Disease recurrence in LLN was rare (3.5% of patients with LLN+ and 0.4% of patients with LLN-). All patients with recurrence in LLN also had distant metastasis. The rate of organ preservation was significantly lower in patients with LLN≥4 mm on restaging MRI (P=0.013). We found no significant differences in rates of local recurrence or metastasis between patients with LLN+ vs. LLN- and in patients with LLN≥7 vs.<7 mm on baseline MRI. LLN dissection was performed in 3 patients; 2 of them died of distant metastasis. CONCLUSIONS: LLN involvement is not associated with disease recurrence or metastasis, but persistence of LLN≥4 mm after TNT is negatively associated with rectum preservation in patients with locally advanced rectal cancer treated with TNT. Dissection of lateral nodes likely benefits few patients.
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PURPOSE: To investigate the differences in baseline staging of anal squamous cell carcinoma based on CT, MRI, and PET/CT, and the resultant impact on the radiation plan. METHODS: This retrospective study included consecutive patients with anal squamous cell carcinoma who underwent baseline pelvic MRI, CT, and PET/CT (all examinations within 3 weeks of each other) from January 2010 to April 2020. CTs, MRIs, and PET/CTs were re-interpreted by three separate radiologists. Several imaging features were assessed; tumor stage was determined based on the eight edition of the American Joint Committee on Cancer (AJCC) staging manual; and T (tumor), N (node), and M (metastasis) categories were determined based on National Comprehensive Cancer Network (NCCN) guidelines. Radiologist assessments were then randomly presented to a radiation oncologist who formulated the radiation plan in a blinded fashion. RESULTS: Across 28 patients (median age, 62 years [range, 31-78], T-category classification was significantly different on PET/CT compared to MRI and CT (p = 0.037 and 0.031, respectively). PET/CT staged a higher proportion of patients with T1/T2 disease (16/28, 57%) compared to MRI (11/28, 39%) and CT (10/28, 36%). MRI staged a higher proportion of patients with T3/T4 disease (14/28, 50%) compared to CT (12/28, 43%) and PET/CT (11/28, 39%). However, there was no significant difference between the three imaging modalities in terms of either N-category, AJCC staging, or NCCN TNM group classification, or in treatment planning. CONCLUSION: Our exploratory study showed that MRI demonstrated a higher proportion of T3/T4 tumors, while PET/CT demonstrated more T1/T2 tumors; however, MRI, CT, and PET/CT did not show any significant differences in AJCC and TNM group categories, nor was there any significant difference in treatment doses between them when assessed independently by an experienced radiation oncologist.
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Neoplasias del Ano , Carcinoma de Células Escamosas , Imagen por Resonancia Magnética , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias del Ano/diagnóstico por imagen , Neoplasias del Ano/radioterapia , Neoplasias del Ano/patología , Femenino , Masculino , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Anciano , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patología , Adulto , Tomografía Computarizada por Rayos X/métodos , Planificación de la Radioterapia Asistida por Computador/métodosRESUMEN
PURPOSE: To evaluate the diagnostic performance of diffusion-weighted imaging (DWI) in the 6-month interval post chemoradiation therapy (CRT) in determining persistent disease and whether persistent diffusion restriction on DWI at 6 months is associated with overall survival; and secondarily, to investigate the accuracy of pelvic lymph node assessment on T2-weighted imaging and DWI in the 6-month interval post CRT, in patients with squamous cell carcinoma of the anus. METHODS AND MATERIALS: This retrospective study included patients with squamous cell carcinoma of the anus who underwent CRT followed by restaging rectal MRI from January 2010 to April 2020, with ≥1 year of follow-up after CRT. DW images were qualitatively evaluated by 2 junior and 2 senior abdominal radiologists to determine anal persistent disease. The reference standard for anal persistent disease was digital rectal examination/endoscopy and histopathology. Diagnostic performance was estimated using sensitivity, specificity, negative predictive value, and positive predictive value. Survival outcomes were evaluated via Kaplan-Meier analysis, and associations between survival outcomes and DWI status were tested for significance using the log-rank test. Additionally, DW and T2-weighted images were evaluated to determine lymph node status. RESULTS: Among 84 patients (mean age, 63 ± 10.2 years; 64/84 [76%] female), 14 of 84 (17%) had confirmed persistent disease. Interreader agreement on DWI between all 4 radiologists was moderate (Light's κ = 0.553). Overall, DWI had a sensitivity of 71.4%, specificity of 72.1%, positive predictive value of 34.5%, and negative predictive value of 92.5%. Patients with a negative DWI showed better survival than patients with a positive DWI (3-year overall survival of 92% vs 79% and 5-year overall survival of 87% vs 74%), although the difference did not reach statistical significance (P = .063). All patients with suspicious lymph nodes (14/14, 100%) showed negative pathology or decreased size during follow-up. CONCLUSIONS: At 6 months post CRT, DWI showed value in excluding anal persistent disease. Persistent diffusion restriction on DWI was not significantly associated with overall survival. Pelvic nodal assessment on DWI and T2-weighted imaging was limited in predicting persistent nodal metastases.
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Neoplasias del Ano , Carcinoma de Células Escamosas , Quimioradioterapia , Imagen de Difusión por Resonancia Magnética , Pelvis , Humanos , Masculino , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Persona de Mediana Edad , Neoplasias del Ano/diagnóstico por imagen , Neoplasias del Ano/terapia , Neoplasias del Ano/patología , Neoplasias del Ano/mortalidad , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidad , Estudios Retrospectivos , Anciano , Pelvis/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Factores de Tiempo , Imagen por Resonancia Magnética/métodos , Metástasis Linfática/diagnóstico por imagen , AdultoRESUMEN
Importance: Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment. Objective: To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade. Design, Setting, and Participants: This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023. Intervention: Patients were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Tumor response was assessed 8 (±4) weeks after TNT by digital rectal examination and endoscopy and categorized by clinical tumor response grade. A 3-tier grading schema that stratifies clinical tumor response into clinical complete response (CCR), near complete response (NCR), and incomplete clinical response (ICR) was devised to maximize patient eligibility for OP. Main Outcomes and Measures: OP and survival rates by clinical tumor response grade were analyzed using the Kaplan-Meier method and log-rank test. Results: There were 304 eligible patients, including 125 patients with a CCR (median [IQR] age, 60.6 [50.4-68.0] years; 76 male [60.8%]), 114 with an NCR (median [IQR] age, 57.6 [49.1-67.9] years; 80 male [70.2%]), and 65 with an ICR (median [IQR] age, 55.5 [47.7-64.2] years; 41 male [63.1%]) based on endoscopic imaging. Age, sex, tumor distance from the anal verge, pathological tumor classification, and clinical nodal classification were similar among the clinical tumor response grades. Median (IQR) follow-up for patients with OP was 4.09 (2.99-4.93) years. The 3-year probability of OP was 77% (95% CI, 70%-85%) for patients with a CCR and 40% (95% CI, 32%-51%) for patients with an NCR (P < .001). Clinical tumor response grade was associated with disease-free survival, local recurrence-free survival, distant metastasis-free survival, and overall survival. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, most patients with a CCR after TNT achieved OP, with few developing tumor regrowth. Although the probability of tumor regrowth was higher for patients with an NCR compared with patients with a CCR, a significant proportion of patients achieved OP. These findings suggest the 3-tier grading schema can be used to estimate recurrence and survival outcomes in patients with locally advanced rectal cancer who receive TNT. Trial Registration: ClinicalTrials.gov Identifier: NCT02008656.
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Adenocarcinoma , Neoplasias Primarias Secundarias , Neoplasias del Recto , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Preservación de Órganos , Neoplasias del Recto/terapia , Adenocarcinoma/terapiaRESUMEN
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656). Patients with stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively (P = .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group (P = .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P = .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.
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Adenocarcinoma , Neoplasias del Recto , Humanos , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Quimioradioterapia/métodos , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Preservación de Órganos , Neoplasias del Recto/tratamiento farmacológico , Resultado del TratamientoRESUMEN
INTRODUCTION: The American Joint Committee on Cancer (AJCC) staging system undergoes periodic revisions to maintain contemporary survival outcomes related to stage. Recently, the AJCC has developed a novel, systematic approach incorporating survival data to refine stage groupings. The objective of this study was to demonstrate data-driven optimization of the version 9 AJCC staging system for anal cancer assessed through a defined validation approach. METHODS: The National Cancer Database was queried for patients diagnosed with anal cancer in 2012 through 2017. Kaplan-Meier methods analyzed 5-year survival by individual clinical T category, N category, M category, and overall stage. Cox proportional hazards models validated overall survival of the revised TNM stage groupings. RESULTS: Overall, 24,328 cases of anal cancer were included. Evaluation of the 8th edition AJCC stage groups demonstrated a lack of hierarchical prognostic order. Survival at 5 years for stage I was 84.4%, 77.4% for stage IIA, and 63.7% for stage IIB; however, stage IIIA disease demonstrated a 73.0% survival, followed by 58.4% for stage IIIB, 59.9% for stage IIIC, and 22.5% for stage IV (p <.001). Thus, stage IIB was redefined as T1-2N1M0, whereas Stage IIIA was redefined as T3N0-1M0. Reevaluation of 5-year survival based on data-informed stage groupings now demonstrates hierarchical prognostic order and validated via Cox proportional hazards models. CONCLUSION: The 8th edition AJCC survival data demonstrated a lack of hierarchical prognostic order and informed revised stage groupings in the version 9 AJCC staging system for anal cancer. Thus, a validated data-driven optimization approach can be implemented for staging revisions across all disease sites moving forward.
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Neoplasias del Ano , Humanos , Estados Unidos/epidemiología , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
Background Diffusion-weighted (DW) imaging is useful in detecting tumor in the primary tumor bed in locally advanced rectal cancer (LARC) after neoadjuvant therapy, but its value in detecting extramural venous invasion (EMVI) and tumor deposit is not well validated. Purpose To evaluate diagnostic accuracy and association with patient prognosis of viable EMVI and tumor deposit on DW images in patients with LARC after neoadjuvant therapy using whole-mount pathology specimens. Materials and Methods This retrospective study included patients who underwent neoadjuvant therapy and surgery from 2018 to 2021. Innovative five-point Likert scale was used by two radiologists to independently evaluate the likelihood of viable EMVI and tumor deposit on restaging DW MRI scans in four axial quadrants (12 to 3 o'clock, 3 to 6 o'clock, 6 to 9 o'clock, and 9 to 12 o'clock). Diagnostic accuracy was assessed at both the per-quadrant and per-patient level, with whole-mount pathology as the reference standard. Weighted κ values for interreader agreement and Cox regression models for disease-free survival and overall survival analyses were used. Results A total of 117 patients (mean age, 56 years ± 12 [SD]; 70 male, 47 female) were included. Pathologically proven viable EMVI and tumor deposit was detected in 29 of 117 patients (25%) and in 44 of 468 quadrants (9.4%). Per-quadrant analyses showed an area under the receiver operating characteristics curve of 0.75 (95% CI: 0.68, 0.83), with sensitivity and specificity of 55% and 96%, respectively. Good interreader agreement was observed between the radiologists (κ = 0.62). Per-patient analysis showed sensitivity and specificity of 62% and 93%, respectively. The presence of EMVI and tumor deposit on restaging DW MRI scans was associated with worse disease-free survival (hazard ratio [HR], 5.6; 95% CI: 2.4, 13.3) and overall survival (HR, 8.9; 95% CI: 1.6, 48.5). Conclusion DW imaging using the five-point Likert scale showed high specificity and moderate sensitivity in the detection of viable extramural venous invasion and tumor deposits in LARC after neoadjuvant therapy, and its presence on restaging DW MRI scans is associated with worse prognosis. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Méndez and Ayuso in this issue.
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Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Masculino , Femenino , Persona de Mediana Edad , Extensión Extranodal , Estudios Retrospectivos , Invasividad Neoplásica/diagnóstico por imagen , Invasividad Neoplásica/patología , Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Imagen por Resonancia Magnética/métodosRESUMEN
PURPOSE: Total neoadjuvant therapy (TNT) is a newly established standard treatment for rectal adenocarcinoma. Current methods to communicate magnitudes of regression during TNT are subjective and imprecise. Magnetic resonance tumor regression grade (MR-TRG) is an existing, but rarely used, regression grading system. Prospective validation of MR-TRG correlation with pathologic response in patients undergoing TNT is lacking. Utility of adding diffusion-weighted imaging to MR-TRG is also unknown. METHODS: We conducted a multi-institutional prospective imaging substudy within NRG-GI002 (ClinicalTrials.gov identifier: NCT02921256) examining the ability of MR-based imaging to predict pathologic complete response (pCR) and correlate MR-TRG with the pathologic neoadjuvant response score (NAR). Serial MRIs were needed from 110 patients. Three radiologists independently, then collectively, reviewed each MRI for complete response (mriCR), which was tested for positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity with pCR. MR-TRG was examined for association with the pathologic NAR score. All team members were blinded to pathologic data. RESULTS: A total of 121 patients from 71 institutions met criteria: 28% were female (n = 34), 84% White (n = 101), and median age was 55 (24-78 years). Kappa scores for T- and N-stage after TNT were 0.38 and 0.88, reflecting fair agreement and near-perfect agreement, respectively. Calling an mriCR resulted in a kappa score of 0.82 after chemotherapy and 0.56 after TNT reflected near-perfect agreement and moderate agreement, respectively. MR-TRG scores were associated with pCR (P < .01) and NAR (P < .0001), PPV for pCR was 40% (95% CI, 26 to 53), and NPV was 84% (95% CI, 75 to 94). CONCLUSION: MRI alone is a poor tool to distinguish pCR in rectal adenocarcinoma undergoing TNT. However, the MR-TRG score presents a now validated method, correlated with pathologic NAR, which can objectively measure regression magnitude during TNT.
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Adenocarcinoma , Neoplasias del Recto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/tratamiento farmacológico , Quimioradioterapia/métodos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/tratamiento farmacológico , Resultado del Tratamiento , Estudios ProspectivosRESUMEN
BACKGROUND: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. METHODS: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. RESULTS: From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. CONCLUSIONS: In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).
Asunto(s)
Neoplasias del Recto , Adulto , Humanos , Canal Anal/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estadificación de Neoplasias , Tratamientos Conservadores del Órgano , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Cuidados Preoperatorios , Periodo PreoperatorioRESUMEN
PURPOSE: The standard of care for locally advanced rectal cancer in North America is neoadjuvant pelvic chemoradiation with fluorouracil (5FUCRT). Neoadjuvant chemotherapy with fluorouracil and oxaliplatin (FOLFOX) is an alternative that may spare patients the morbidity of radiation. Understanding the relative patient experiences with these options is necessary to inform treatment decisions. METHODS: PROSPECT was a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX versus 5FUCRT, which enrolled adults with rectal cancer clinically staged as T2N+, cT3N-, or cT3N+ who were candidates for sphincter-sparing surgery. Neoadjuvant FOLFOX was given in six cycles over 12 weeks, followed by surgery. Neoadjuvant 5FUCRT was delivered in 28 fractions over 5.5 weeks, followed by surgery. Adjuvant chemotherapy was suggested but not mandated in both groups. Enrolled patients were asked to provide patient-reported outcomes (PROs) at baseline, during neoadjuvant treatment, and at 12 months after surgery. PROs included 14 symptoms from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Additional PRO instruments measured bowel, bladder, sexual function, and health-related quality of life (HRQL). RESULTS: From June 2012 to December 2018, 1,194 patients were randomly assigned, 1,128 initiated treatment, and 940 contributed PRO-CTCAE data (493 FOLFOX; 447 5FUCRT). During neoadjuvant treatment, patients reported significantly lower rates of diarrhea and better overall bowel function with FOLFOX while anxiety, appetite loss, constipation, depression, dysphagia, dyspnea, edema, fatigue, mucositis, nausea, neuropathy, and vomiting were lower with 5FUCRT (all multiplicity adjusted P < .05). At 12 months after surgery, patients randomly assigned to FOLFOX reported significantly lower rates of fatigue and neuropathy and better sexual function versus 5FUCRT (all multiplicity adjusted P < .05). Neither bladder function nor HRQL differed between groups at any time point. CONCLUSION: For patients with locally advanced rectal cancer choosing between neoadjuvant FOLFOX and 5FUCRT, the distinctive PRO profiles inform treatment selection and shared decision making.
Asunto(s)
Canal Anal , Neoplasias del Recto , Adulto , Humanos , Canal Anal/patología , Calidad de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estadificación de Neoplasias , Tratamientos Conservadores del Órgano , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Fluorouracilo , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/métodos , Medición de Resultados Informados por el Paciente , Leucovorina , Resultado del TratamientoRESUMEN
The National Accreditation Program for Rectal Cancer (NAPRC) was established by the American College of Surgeons with the goal of standardizing care of rectal cancer patients in order to improve outcomes. NAPRC accreditation requires compliance with an established set of standards, many of which are directly related to radiology participation in multidisciplinary conference, rectal MR image acquisition, interpretation and reporting, and radiologist education. This paper outlines the pertinent standards/requirements for radiologists as part of the Rectal Cancer Multidisciplinary Team in the NAPRC guidelines, with proposed methods and tips for implementation of these standards from the perspective of the radiologist.
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Radiología , Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/cirugía , Acreditación , RadiólogosRESUMEN
Total neoadjuvant treatment (TNT) for rectal cancer is becoming an accepted treatment paradigm and is changing the landscape of this disease, wherein up to 50% of patients who undergo TNT are able to avoid surgery. This places new demands on the radiologist in terms of interpreting degrees of response to treatment. This primer summarizes the Watch-and-Wait approach and the role of imaging, with illustrative "atlas-like" examples as an educational guide for radiologists. We present a brief literature summary of the evolution of rectal cancer treatment, with a focus on magnetic resonance imaging (MRI) assessment of response. We also discuss recommended guidelines and standards. We outline the common TNT approach entering mainstream practice. A heuristic and algorithmic approach to MRI interpretation is also offered. To illustrate management and common scenarios, we arranged the illustrative figures as follows: (I) Clinical complete response (cCR) achieved at the immediate post-TNT "decision point" scan time; (II) cCR achieved at some point during surveillance, later than the first post-TNT MRI; (III) near clinical complete response (nCR); (IV) incomplete clinical response (iCR); (V) discordant findings between MRI and endoscopy where MRI is falsely positive, even at follow-up; (VI) discordant cases where MRI seems to be falsely positive but is proven truly positive on follow-up endoscopy; (VII) cases where MRI is falsely negative; (VIII) regrowth of tumor in the primary tumor bed; (IX) regrowth outside the primary tumor bed; and (X) challenging scenarios, i.e., mucinous cases. This primer is offered to achieve its intended goal of educating radiologists on how to interpret MRI in patients with rectal cancer undergoing treatment using a TNT-type treatment paradigm and a Watch-and-Wait approach.
Asunto(s)
Neoplasias del Recto , Humanos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Recto/patología , Terapia Neoadyuvante , Endoscopía Gastrointestinal , Imagen por Resonancia Magnética , Recurrencia Local de Neoplasia/terapia , Resultado del TratamientoRESUMEN
The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including anal cancer, is the standard for cancer staging in the United States. The AJCC staging criteria are dynamic, and periodic updates are conducted to optimize AJCC staging definitions through a panel of experts charged with evaluating new evidence to implement changes. With greater availability of large data sets, the AJCC has since restructured and updated its processes, incorporating prospectively collected data to validate stage group revisions in the version 9 AJCC staging system, including anal cancer. Survival analysis using AJCC eighth edition staging guidelines revealed a lack of hierarchical order in which stage IIIA anal cancer was associated with a better prognosis than stage IIB disease, suggesting that, for anal cancer, tumor (T) category has a greater effect on survival than lymph node (N) category. Accordingly, version 9 stage groups have been appropriately adjusted to reflect contemporary long-term outcomes. This article highlights the changes to the now published AJCC staging system for anal cancer, which: (1) redefined stage IIB as T1-T2N1M0 disease, (2) redefined stage IIIA as T3N0-N1M0 disease, and (3) eliminated stage 0 disease from its guidelines altogether.
Asunto(s)
Neoplasias del Ano , Humanos , Estados Unidos , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Neoplasias del Ano/diagnósticoRESUMEN
BACKGROUND. Patients with nonmucinous rectal adenocarcinoma may develop mucinous changes after neoadjuvant chemoradiotherapy, which are described as mucinous degeneration. The finding's significance in earlier studies has varied. OBJECTIVE. The purpose of this study was to assess the frequency of mucinous degeneration on MRI after neoadjuvant therapy for rectal adenocarcinoma and to compare outcomes among patients with nonmucinous tumor, mucinous tumor, and mucinous degeneration on MRI. METHODS. This retrospective study included 201 patients (83 women, 118 men; mean age, 61.8 ± 2.2 [SD] years) with rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision from October 2011 to November 2015, underwent baseline and restaging rectal MRI examinations, and had at least 2 years of follow-up. Two radiologists independently evaluated MRI examinations for mucin content, which was defined as T2 hyperintensity in the tumor or tumor bed, and resolved differences by consensus. Patients were classified into three groups on the basis of mucin status: those with nonmucinous tumor (≤ 50% mucin content on baseline and restaging examinations), those with mucinous tumor (> 50% mucin content on baseline and restaging examinations), and those with mucinous degeneration (≤ 50% mucin content on baseline examination and > 50% content on restaging examination). The three groups were compared. RESULTS. Interreader agreement for mucin content, expressed as a kappa coefficient, was 0.893 on baseline MRI and 0.890 on restaging MRI. Of the 201 patients, 156 (77.6%) had nonmucinous tumor, 34 (16.9%) had mucinous tumor, and 11 (5.5%) had mucinous degeneration. Mucin status was not significantly associated with complete pathologic response (p = .41) or local or distant recurrence (both p > .05). The death rate during follow-up was not significantly different (p = .21) between patients with nonmucinous tumor (23.1%), those with mucinous tumor (29.4%), and those with mucinous degeneration (9.1%). In adjusted Cox regression analysis, with mucinous degeneration used as reference, the HR for the overall survival rate for the mucinous tumor group was 4.7 (95% CI, 0.6-38.3; p = .14), and that for the nonmucinous tumor group was 8.0 (95% CI, 0.9-59.9; p = .06). On histopathologic assessment, all 11 patients with mucinous degeneration showed acellular mucin, yet 10 of 11 patients showed viable tumor (i.e., in nonmucinous portions of the tumors). CONCLUSION. Mucinous degeneration on MRI is not significantly associated with pathologic complete response, recurrence, or survival. CLINICAL IMPACT. Mucinous degeneration on MRI is uncommon and should not be deemed an indicator of pathologic complete response.
Asunto(s)
Adenocarcinoma Mucinoso , Neoplasias del Recto , Masculino , Humanos , Femenino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Resultado del Tratamiento , Estudios Retrospectivos , Adenocarcinoma Mucinoso/diagnóstico por imagen , Adenocarcinoma Mucinoso/terapia , Quimioradioterapia/métodos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Imagen por Resonancia Magnética , Mucinas , Estadificación de NeoplasiasRESUMEN
The role and method of image-based staging of anal cancer has evolved with the rapid development of newer imaging modalities and the need to address the rising incidence of this rare cancer. In 2014, the European Society of Medical Oncology mandated pelvic magnetic resonance imaging (MRI) for anal cancer and subsequently other societies such as the National Comprehensive Cancer Network followed suit with similar recommendations. Nevertheless, great variability exists from center to center and even within individual centers. Notably, this is in stark contrast to the imaging of the anatomically nearby rectal cancer. As participating team members for this malignancy, we embarked on a comprehensive literature review of anal cancer imaging to understand the relative merits of these new technologies which developed after computed tomography (CT), e.g., MRI and positron emission tomography/computed tomography (PET/CT). The results of this literature review helped to inform our next stage: questionnaire development regarding the imaging of anal cancer. Next, we distributed the questionnaire to members of the Society of Abdominal Radiology (SAR) Rectal and Anal Disease-Focused Panel, a group of abdominal radiologists with special interest, experience, and expertise in rectal and anal cancer, to provide expert radiologist opinion on the appropriate anal cancer imaging strategy. In our expert opinion survey, experts advocated the use of MRI in general (65% overall and 91-100% for primary staging clinical scenarios) and acknowledged the superiority of PET/CT for nodal assessment (52-56% agreement for using PET/CT in primary staging clinical scenarios compared to 30% for using MRI). We therefore support the use of MRI and PET and suggest further exploration of PET/MRI as an optimal combined evaluation. Our questionnaire responses emphasized the heterogeneity in imaging practice as performed at numerous academic cancer centers across the United States and underscore the need for further reconciliation and establishment of best imaging practice guidelines for optimized patient care in anal cancer.