RESUMEN
BACKGROUND: The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. METHODS: This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. DISCUSSION: This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04838496 , registered on 02-04-2021 Netherlands Trial Register: NL9790. PROTOCOL VERSION: Version 3 dd 11-4-2022.
Asunto(s)
Neoplasias Primarias Secundarias , Neoplasias del Recto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/análogos & derivados , Quimioradioterapia/métodos , Ensayos Clínicos Fase II como Asunto , Fluorouracilo/uso terapéutico , Humanos , Leucovorina , Estudios Multicéntricos como Asunto , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/patología , Compuestos Organoplatinos , Calidad de Vida , Neoplasias del Recto/patología , Resultado del TratamientoRESUMEN
BACKGROUND: In patients with rectal cancer, enlarged lateral lymph nodes (LLNs) result in increased lateral local recurrence (LLR) and lower cancer-specific survival (CSS) rates, which can be improved with (chemo)radiotherapy ((C)RT) and LLN dissection (LLND). This study investigated whether different LLN locations affect oncological outcomes. METHODS: Patients with low cT3-4 rectal cancer without synchronous distant metastases were included in this multicentre retrospective cohort study. All MRI was re-evaluated, with special attention to LLN involvement and response. RESULTS: More advanced cT and cN category were associated with the occurrence of enlarged obturator nodes. Multivariable analyses showed that a node in the internal iliac compartment with a short-axis (SA) size of at least 7 mm on baseline MRI and over 4 mm after (C)RT was predictive of LLR, compared with a post-(C)RT SA of 4 mm or less (hazard ratio (HR) 5.74, 95 per cent c.i. 2.98 to 11.05 vs HR 1.40, 0.19 to 10.20; P < 0.001). Obturator LLNs with a SA larger than 6 mm after (C)RT were associated with a higher 5-year distant metastasis rate and lowered CSS in patients who did not undergo LLND. The survival difference was not present after LLND. Multivariable analyses found that only cT category (HR 2.22, 1.07 to 4.64; P = 0.033) and margin involvement (HR 2.95, 1.18 to 7.37; P = 0.021) independently predicted the development of metastatic disease. CONCLUSION: Internal iliac LLN enlargement is associated with an increased LLR rate, whereas obturator nodes are associated with more advanced disease with increased distant metastasis and reduced CSS rates. LLND improves local control in persistent internal iliac nodes, and might have a role in controlling systemic spread in persistent obturator nodes.Members of the Lateral Node Study Consortium are co-authors of this study and are listed under the heading Collaborators.
Asunto(s)
Metástasis Linfática/patología , Neoplasias del Recto/patología , Anciano , Femenino , Humanos , Escisión del Ganglio Linfático/mortalidad , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/terapia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pelvis , Neoplasias del Recto/mortalidad , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
AIM: Outcomes in elderly patients (≥75 years) with non-advanced colorectal cancer have improved. It is unclear whether this is also true for elderly patients with clinical T4 rectal cancer (cT4RC) or locally recurrent rectal cancer (LRRC). We aimed to compare age-related differences in morbidity and mortality after curative treatment for cT4RC and LRRC. METHODS: All cT4RC and LRRC patients without distant metastasis who underwent curative surgery between 2005 and 2017 in the Catharina Hospital (Eindhoven, The Netherlands) were included. Morbidity and mortality were evaluated based on age (<75 and ≥75 years) and date of surgery (2005-2011 and 2012-2017). RESULTS: Overall, 72 of 474 (15.2%) cT4RC and 53 of 293 (18.1%) LRRC patients were ≥75 years. No significant differences in the incidence of Clavien-Dindo I-IV complications were observed between age groups. However, in elderly cT4RC patients, cerebrovascular accidents occurred more frequently (4.2% vs. 0.5%, P = 0.03). Between 2005-2011 and 2012-2017, 30-day mortality improved from 7.5% to 3.1% and from 10.0% to 0.0% in elderly cT4RC and LRRC patients, respectively. The 1-year mortality during 2012-2017 was worse in elderly than in younger patients (28.1% vs. 6.2%, P = 0.001 for cT4RC and 27.3% vs. 13.8%, P = 0.06 for LRRC). In elderly cT4RC and LRRC patients, 44.4% and 46.2% died due to non-cancer-related causes, while only 27.8% and 23.1% died due to disease recurrence, respectively. CONCLUSION: Although the 30-day mortality in elderly cT4RC and LRRC patients improved after curative treatment, the 1-year mortality in elderly patients continued to be high, which requires more awareness for the elderly after hospitalization.
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Recurrencia Local de Neoplasia , Neoplasias del Recto , Anciano , Humanos , Morbilidad , Recurrencia Local de Neoplasia/epidemiología , Países Bajos/epidemiología , Neoplasias del Recto/cirugíaRESUMEN
AIM: Patients with locally recurrent rectal cancer (LRRC) frequently present with either synchronous metastases or a history of metastases. This study was conducted to evaluate whether LRRC patients without metastases have a different oncological outcome compared to patients with a history of metastases treated with curative intent or patients with potentially curable synchronous metastases. METHOD: All consecutive LRRC patients who underwent intentionally curative surgery between 2005 and 2017 in a large tertiary hospital were retrospectively reviewed and categorized as having no metastases, a history of (curatively treated) metastases or synchronous metastases. Patients with unresectable distant metastases were excluded from the analysis. RESULTS: Of the 349 patients who were analysed, 261 (75%) had no metastases, 42 (12%) had a history of metastases and 46 (13%) had synchronous metastases. The 3-year metastasis-free survival was 52%, 33% and 13% in patients without metastases, with a history of metastases, and with synchronous metastases, respectively (P < 0.001) A history of metastases did not influence overall survival (OS), but there was a trend towards a worse OS in patients with synchronous metastases compared with patients without synchronous metastases (hazard ratio 1.43; 95% CI 0.98-2.11). CONCLUSION: LRRC patients with a history of curatively treated metastases have an OS comparable to that in patients without metastases and should therefore be treated with curative intent. However, LRRC patients with synchronous metastases have a poor metastasis-free survival and worse OS; in these patients, an individualized treatment approach to observe the behaviour of the disease is recommended.
Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias del Recto , Humanos , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias del Recto/terapia , Recto , Estudios RetrospectivosRESUMEN
BACKGROUND: Despite improvements in the multimodality treatment for patients with locally recurrent rectal cancer (LRRC), oncological outcomes remain poor. This study evaluated the effect of induction chemotherapy and subsequent chemo(re)irradiation on the pathologic response and the rate of resections with clear margins (R0 resection) in relation to long-term oncological outcomes. METHODS: All consecutive patients with LRRC treated in the Catharina Hospital Eindhoven who underwent a resection after treatment with induction chemotherapy and subsequent chemo(re)irradiation between January 2010 and December 2018 were retrospectively reviewed. Induction chemotherapy consisted of CAPOX/FOLFOX. Endpoints were pathologic response, resection margin and overall survival (OS), disease free survival (DFS), local recurrence free survival (LRFS), and metastasis free survival (MFS). RESULTS: A pathologic complete response was observed in 22 patients (17%), a "good" response (Mandard 2-3) in 74 patients (56%), and a "poor" response (Mandard 4-5) in 36 patients (27%). An R0 resection was obtained in 83 patients (63%). The degree of pathologic response was linearly correlated with the R0 resection rate (p = 0.026). In patients without synchronous metastases, pathologic response was an independent predictor for LRFS, MFS, and DFS (p = 0.004, p = 0.003, and p = 0.024, respectively), whereas R0 resection was an independent predictor for LRFS and OS (p = 0.020 and p = 0.028, respectively). CONCLUSIONS: Induction chemotherapy in addition to neoadjuvant chemo(re)irradiation is a promising treatment strategy for patients with LRRC with high pathologic response rates that translate into improved oncological outcomes, especially when an R0 resection has been achieved.
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Quimioterapia de Inducción , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Neoplasias del Recto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/administración & dosificación , Terapia Combinada , Femenino , Fluorouracilo/administración & dosificación , Humanos , Quimioterapia de Inducción/métodos , Leucovorina/administración & dosificación , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino/administración & dosificación , Proctectomía/métodos , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/mortalidad , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Reoperación , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: The optimal treatment sequence for patients with rectal cancer and synchronous liver metastases remains unclear. The aim of this study was to evaluate the feasibility and effectiveness of short-course pelvic radiotherapy (5 × 5 Gy) followed by systemic therapy and local treatment of all tumour sites in patients with potentially curable stage IV rectal cancer in daily practice. METHODS: This was a retrospective study performed in eight tertiary referral centres in the Netherlands. Patients aged 18 years or above with rectal cancer and potentially resectable liver ± extrahepatic metastases, treated between 2010 and 2015, were eligible. Main outcomes included full completion of treatment schedule, symptom control and survival. RESULTS: In total, 169 patients were included with a median follow-up of 49·5 (95 pr cent c.i. 43·6 to 55·6) months. The completion rate for the entire treatment schedule was 65·7 per cent. Three-year progression-free survival and overall survival (OS) rates were 24·2 (95 per cent c.i. 16·6 to 31·6) and 48·8 (40·4 to 57·2) per cent respectively. Median OS of patients who responded well and completed the treatment schedule was 51·5 months, compared with 15·1 months for patients who did not complete the treatment (P < 0·001). Adequate symptom control of the primary tumour was achieved in 87·0 per cent of all patients. CONCLUSION: Multimodal treatment leads to relief of symptoms in most patients, and is associated with good survival rates in those able to complete the schedule. [Correction added on 12 February 2020, after first online publication: the Conclusion has been reworded for clarity].
ANTECEDENTES: La secuencia óptima de tratamiento en pacientes con cáncer de recto y metástasis hepáticas sincrónicas sigue sin estar clara. El objetivo de este estudio fue evaluar en la práctica diaria la viabilidad y efectividad de la radioterapia pélvica de ciclo corto (5 x 5 Gy) seguida de tratamiento sistémico y tratamiento local de todas las localizaciones del tumor primario en pacientes con cáncer de recto estadio IV potencialmente curables. MÉTODOS: Estudio retrospectivo realizado en ocho centros terciarios de referencia en Holanda. Se consideró elegibles a los pacientes mayores de 18 años con cáncer de recto y metástasis hepáticas ± extrahepáticas potencialmente resecables, que fueron tratados entre 2010 y 2015. Los criterios de valoración principales incluyeron la finalización completa del programa de tratamiento, el control de los síntomas y la supervivencia. RESULTADOS: En total se incluyeron 169 pacientes con una mediana de seguimiento de 50 meses (rango 2-89 meses). La tasa de finalización del programa de tratamiento completo fue del 65,7%. Las tasas de supervivencia libre de progresión a 3 años y supervivencia global (overall survival, OS) fueron 24,2% (i.c. del 95% 16,6-31,6) y 48,8% (i.c. del 95% 40,4-57,2), respectivamente. La mediana de OS de los pacientes que respondieron bien y completaron el programa de tratamiento fue de 51,5 meses, en comparación con 15,1 meses en pacientes que no completaron el tratamiento (P < 0,001). Se logró un control adecuado de los síntomas del tumor primario en el 87,0% de todos los pacientes. CONCLUSIÓN: El tratamiento multimodal consigue paliar los síntomas en la mayoría de los pacientes y se asocia con buenas tasas de supervivencia en aquellos pacientes que pueden completar el programa.
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Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/efectos adversos , Estudios de Factibilidad , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Estadificación de Neoplasias , Proctectomía , Supervivencia sin Progresión , Radioterapia Adyuvante/efectos adversos , Neoplasias del Recto/patología , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
AIM: Low anterior resection syndrome (LARS) severely affects the quality of life (QoL) of patients after surgery for rectal cancer. There are very few studies that have investigated LARS-like symptoms and their effect on QoL after colon cancer surgery. The aim of this study was to investigate the prevalence of functional abdominal complaints and related QoL after colon cancer surgery compared with patients with similar complaints after rectal cancer surgery. METHOD: All patients who underwent colorectal cancer resections between January 2008 and December 2015, and who were free of colostomy for at least 1 year, were eligible (n = 2136). Bowel function was assessed by the LARS score, QoL by the EORTC QLQ-C30 and QLQ-CR29 questionnaires. QoL was compared between the LARS score categories and tumour height categories. RESULTS: A total of 1495 patients (70.0%) were included in the analyses, of whom 1145 had a colonic and 350 a rectal tumour. Symptoms of LARS were observed in 55% after rectal cancer resection compared with 21% after colon cancer resection. Female gender (OR 1.88, CI 1.392-2.528) and a previous diverting stoma (OR 1.84, CI 1.14-2.97) were independently associated with a higher prevalence of LARS after colon cancer surgery. Patients with LARS after colon cancer surgery performed significantly worse in most QoL domains. CONCLUSION: The results of this study highlight the presence of LARS-like symptoms after surgery for colonic cancer. Patients suffering from major LARS-like symptoms after colon resection reported the same debilitating effect on their QoL as patients with major LARS after rectal resection. This should be addressed by colorectal cancer specialists in order to adequately inform patients.
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Colectomía/psicología , Neoplasias del Colon/cirugía , Enfermedades Gastrointestinales/epidemiología , Complicaciones Posoperatorias/epidemiología , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Colectomía/efectos adversos , Neoplasias del Colon/psicología , Estudios Transversales , Defecación , Femenino , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/psicología , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/psicología , Prevalencia , Proctectomía/efectos adversos , Proctectomía/psicología , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Síndrome , Resultado del TratamientoRESUMEN
BACKGROUND: Ipsilateral breast tumour recurrence (IBTR) has an unfavourable prognosis, with a significant subsequent risk of distant recurrence. Repeat sentinel lymph node biopsy (rSLNB) has recently been demonstrated to be technically feasible and useful in tailoring adjuvant treatment plans in patients with IBTR. The prognostic impact of rSLNB in patients with IBTR remains unclear. This study analysed the risk of distant recurrence after IBTR, and evaluated the prognostic impact of rSLNB and other patient and tumour characteristics on distant recurrence-free survival. METHODS: Data were obtained from the SNARB (Sentinel Node and Recurrent Breast Cancer) study. Cox proportional hazards analyses were performed to assess the prognostic effect of tumour, patient and treatment factors on distant recurrence-free survival. RESULTS: Of the 515 included patients, 230 (44·7 per cent) had a tumour-negative rSLNB and 46 (8·9 per cent) a tumour-positive rSLNB. In 239 patients (46·4 per cent) the rSLNB procedure was unsuccessful. After a median follow-up of 5·1 years, 115 patients (22·3 per cent) had developed a recurrence. The overall 5-year distant recurrence-free survival rate was 84·2 (95 per cent c.i. 80·7 to 87·7) per cent. An interval of less than 2 years between primary breast cancer treatment and ipsilateral recurrence (P = 0·018), triple-negative IBTR (P = 0·045) and absence of adjuvant chemotherapy after IBTR (P = 0·010) were independently associated with poor distant recurrence-free survival. The association between the outcome of rSLNB and distant recurrence-free survival was not statistically significant (P = 0·682). CONCLUSION: The outcome of rSLNB is not an important prognostic factor for distant recurrence, and its value as a staging tool in patients with IBTR seems disputable.
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Neoplasias de la Mama/patología , Recurrencia Local de Neoplasia/patología , Biopsia del Ganglio Linfático Centinela , Adulto , Anciano , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Factores de TiempoRESUMEN
BACKGROUND: Synchronous colorectal carcinomas (CRC) occur in 1-8% of patients diagnosed with CRC. This study evaluated treatment patterns and patient outcomes in synchronous CRCs compared with solitary CRC patients. METHODS: All patients diagnosed with primary CRC between 2008 and 2013, who underwent elective surgery, were selected from the Netherlands Cancer Registry. Using multivariable regressions, the effects of synchronous CRC were assessed for both short-term outcomes (prolonged postoperative hospital admission, anastomotic leakage, postoperative 30-day mortality, administration of neoadjuvant or adjuvant treatment), and 5-year relative survival (RS). RESULTS: Of 41,060 CRC patients, 1969 patients (5%) had synchronous CRC. Patients with synchronous CRC were older (mean age 71 ± 10.6 vs. 69 ± 11.4 years), more often male (61 vs. 54%), and diagnosed with more advanced tumour stage (stage III-IV 54 vs. 49%) compared with solitary CRC (all p < 0.0001). In 50% of the synchronous CRCs, an extended surgery was conducted (n = 934). Synchronous CRCs with at least one stage II-III rectal tumour less likely received neoadjuvant (chemo)radiation [78 vs. 86%; adjusted OR 0.6 (0.48-0.84)], and synchronous CRCs with at least one stage III colon tumour less likely received adjuvant chemotherapy [49 vs. 63%; adjusted OR 0.7 (0.55-0.89)]. Synchronous CRCs were independently associated with decreased survival [RS 77 vs. 71%; adjusted RER 1.1 (1.01-1.23)]. CONCLUSIONS: The incidence of synchronous CRCs in the Dutch population is 5%. Synchronous CRCs were associated with decreased survival compared with solitary CRC. The results emphasize the importance of identifying synchronous tumours, preferably before surgery to provide optimal treatment.
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Neoplasias Colorrectales/cirugía , Cirugía Colorrectal/mortalidad , Neoplasias Primarias Múltiples/cirugía , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/epidemiología , Neoplasias Primarias Múltiples/patología , Países Bajos/epidemiología , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: A significant number of patients treated for locally recurrent rectal cancer have local or systemic failure, especially after incomplete surgical resection. Neoadjuvant treatment regimens in patients who have already undergone preoperative (chemo)radiotherapy for the primary tumour are limited. The objective of the present study was to evaluate the influence of a neoadjuvant regimen incorporating induction chemotherapy (ICT) in patients with locally recurrent rectal cancer who had preoperative (chemo)radiotherapy for the primary cancer or an earlier local recurrence. METHODS: Patients were treated with a sequential neoadjuvant regimen including three or four cycles of 5-fluorouracil and oxaliplatin-containing chemotherapy. When no progressive disease was found at evaluation, neoadjuvant treatment was continued with chemoradiation therapy (CRRT) using 30 Gy with concomitant capecitabine. If there was a response to ICT, the patient was advised to continue with systemic chemotherapy after CRRT as consolidation chemotherapy while waiting for resection. These patients were compared with patients who received CRRT alone in the same time interval. RESULTS: Of 58 patients who had ICT, 32 (55 per cent) had surgery with clear resection margins, of whom ten (17 per cent) exhibited a pathological complete response (pCR). The remaining 26 patients had 23 R1 and three R2 resections. In 71 patients who received CRRT, a similar rate of R0 (35 patients) and R1 (36) resection was found (P = 0·506), but only three patients (4 per cent) had a pCR (P = 0·015). CONCLUSION: The incorporation of ICT in neoadjuvant regimens for locally recurrent rectal cancer is a promising strategy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Inducción , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Quimioradioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Neoplasias del Recto/terapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Lateral nodal disease in rectal cancer remains a subject of debate and is treated differently in the East and the West. The predictive value of lateral lymph node and MRI-detected extramural vascular invasion (mrEMVI) features on oncological outcomes was assessed in this study. METHODS: In this retrospective cohort study, data on patients with cT3-4 rectal cancer within 8 cm from the anal verge were considered over a 5-year period (2009-2013). Lateral lymph node size, malignant features and mrEMVI features were evaluated and related to oncological outcomes. RESULTS: In total, 192 patients were studied, of whom 30 (15·6 per cent) underwent short-course radiotherapy and 145 (75·5 per cent) received chemoradiotherapy. A lateral lymph node short-axis size of 10 mm or more was associated with a significantly higher 5-year lateral/presacral local recurrence rate of 37 per cent, compared with 7·7 per cent in nodes smaller than 10 mm (P = 0·041). Enlarged nodes did not result in a higher 5-year rate of distant metastasis (23 per cent versus 27·7 per cent in nodes smaller than 10 mm; P = 0·563). However, mrEMVI positivity was related to more metastatic disease (5-year rate 43 versus 26·3 per cent in the mrEMVI-negative group; P = 0·014), but not with increased lateral/presacral recurrence. mrEMVI occurred in 46·6 per cent of patients with nodes smaller than 10 mm, compared with 29 per cent in patients with nodes of 10 mm or larger (P = 0·267). CONCLUSION: Although lateral nodal disease is more a local problem, mrEMVI mainly predicts distant recurrence. The results of this study showed an unacceptably high local recurrence rate in patients with a short axis of 10 mm or more, despite neoadjuvant (chemo)radiotherapy.
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Ganglios Linfáticos/patología , Neoplasias del Recto/patología , Neoplasias Vasculares/patología , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante/mortalidad , Quimioterapia Adyuvante/estadística & datos numéricos , Femenino , Humanos , Metástasis Linfática , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/mortalidad , Terapia Neoadyuvante/estadística & datos numéricos , Invasividad Neoplásica , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Países Bajos/epidemiología , Tamaño de los Órganos , Pronóstico , Radioterapia Adyuvante/mortalidad , Radioterapia Adyuvante/estadística & datos numéricos , Neoplasias del Recto/mortalidad , Neoplasias del Recto/terapia , Estudios Retrospectivos , Neoplasias Vasculares/mortalidad , Neoplasias Vasculares/terapiaRESUMEN
BACKGROUND: In a Dutch phase II trial conducted between 2006 and 2010, short-course radiotherapy followed by systemic therapy with capecitabine, oxaliplatin, and bevacizumab as neoadjuvant treatment and subsequent radical surgical treatment of primary tumor and metastatic sites was evaluated. In this study, we report the long-term results after a minimum follow-up of 6 years. METHODS: Patients with histologically confirmed rectal adenocarcinoma with potentially resectable or ablatable metastases in liver or lungs were eligible. Follow-up data were collected for all patients enrolled in the trial. Overall and recurrence-free survival were calculated using the Kaplan-Meier method. RESULTS: Follow-up data were available for all 50 patients. After a median follow-up time of 8.1 years (range 6.0-9.8), 16 patients (32.0%) were still alive and 14 (28%) were disease-free. The median overall survival was 3.8 years (range 0.5-9.4). From the 36 patients who received radical treatment, two (5.6%) had a local recurrence and 29 (80.6%) had a distant recurrence. CONCLUSIONS: Long-term survival can be achieved in patients with primary metastatic rectal cancer after neoadjuvant radio- and chemotherapy. Despite a high number of recurrences, 32% of patients were alive after a median follow-up time of 8.1 years.
Asunto(s)
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/secundario , Neoplasias del Recto/terapia , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Adulto , Anciano , Bevacizumab/administración & dosificación , Capecitabina/administración & dosificación , Quimioradioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Dosificación Radioterapéutica , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Tasa de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) can result in long-term survival for selected patients with colorectal peritoneal metastases (PM). Most patients are additionally treated with systemic chemotherapy, but timing (adjuvant vs. preoperative) varies between treatment centers. This study aimed to compare short- and long-term outcomes for patients with synchronous colorectal PM undergoing CRS + HIPEC who received preoperative or adjuvant chemotherapy. METHODS: This study enrolled patients with synchronous colorectal PM who underwent macroscopically complete or near complete CRS + HIPEC. Data were collected from a prospective database containing all patients between 2007 and 2014. Perioperative outcome and survival were compared between patients who underwent adjuvant chemotherapy (adjuvant strategy [AS]) and those who had preoperative chemotherapy followed by adjuvant systemic chemotherapy if possible (preoperative strategy [PS]). RESULTS: The study enrolled 91 patients, 25 (28 %) of whom received preoperative chemotherapy. The peritoneal cancer index (PCI) score was lower and the operation length shorter for the patients receiving preoperative chemotherapy (both p = 0.02). The complication rates were comparable between the two groups. The median survival after diagnosis was 38.6 months in the AS group, whereas median survival was not reached in the PS group (p < 0.01). The 3-year overall survival rates were 50 and 89 %, respectively. After correction for other significant prognostic factors, preoperative chemotherapy was independently associated with improved survival (HR 0.23; 95 % confidence interval, 0.07-0.75; p = 0.01). CONCLUSION: Treatment with preoperative chemotherapy was associated with improved long-term survival after CRS + HIPEC compared with adjuvant chemotherapy. Ideally, a randomized controlled trial should be performed to investigate the optimal timing of systemic chemotherapy for colorectal PM patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/patología , Hipertermia Inducida , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Anciano , Quimioterapia Adyuvante , Procedimientos Quirúrgicos de Citorreducción , Femenino , Humanos , Infusiones Parenterales , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoAsunto(s)
Quimioterapia de Inducción/métodos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Terapia Combinada , Supervivencia sin Enfermedad , Humanos , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Neoplasias del Recto/mortalidad , Neoplasias del Recto/cirugía , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
AIM: Dissection of the perineal body (PB) during abdominoperineal excision (APE) for low rectal cancer is often difficult due to the lack of a natural plane of dissection. Understanding the PB and its relation to the anorectum is essential to permit safe dissection during the perineal phase of the operation and avoid damage to the anorectum and urogenital organs. This study describes the anatomy and histology of the PB relevant to APE. METHOD: Six human adult cadaver pelvic exenteration specimens (three male, three female) from the Leeds GIFT Research Tissue Programme were studied. Paraffin-embedded mega-blocks were produced and serially sectioned at 50- and 250-µm intervals. Sections were stained by immunohistochemistry to show collagen, elastin and smooth muscle. RESULTS: The PB was cylindrically shaped in the male specimens and wedge-shaped in the female ones. Although centrally located between the anal and urogenital triangles, it was nearly completely formed by muscle fibres derived from the rectal muscularis propria. Thick bundles of smooth muscle, mostly arising from the longitudinal muscle, inserted into the PB and levator ani muscle (LAM). The recto-urethralis muscle originated from the PB and separated the anterolateral PB from the urogenital organs. CONCLUSION: Smooth muscle fibres derived from the rectal muscularis propria extend into the PB and LAM and appear to fix the anorectum. Dissection of the PB during APE is safe only when the smooth muscle fibres that extend into the PB are divided.
Asunto(s)
Abdomen/cirugía , Exenteración Pélvica/métodos , Perineo/anatomía & histología , Perineo/cirugía , Neoplasias del Recto/cirugía , Cadáver , Disección/métodos , Femenino , Humanos , Masculino , Músculo Liso/anatomía & histología , Neoplasias del Recto/patología , Recto/anatomía & histología , Uretra/anatomía & histologíaRESUMEN
BACKGROUND: The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME). PATIENTS AND METHODS: The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. RESULTS: Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). CONCLUSION: The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual. REGISTRATION NUMBER: Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/epidemiología , Neoplasias del Recto/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/terapia , Capecitabina/administración & dosificación , Quimioterapia Adyuvante , Terapia Combinada , Procedimientos Quirúrgicos del Sistema Digestivo , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Incidencia , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Países Bajos/epidemiología , Pronóstico , Radioterapia Adyuvante , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Tasa de SupervivenciaRESUMEN
Most patients with locally recurrent breast cancer undergo axillary lymph node dissection (ALND). However, repeat sentinel node biopsy (SNB) could provide regional nodal staging and obviate the need for standard ALND. The Sentinel Node and Recurrent Breast Cancer (SNARB) study is a Dutch nationwide registration study conducted to determine feasibility, aberrant drainage rates, and clinical consequences of repeat SNB. A total of 536 patients with locally recurrent non-metastatic breast cancer underwent lymphatic mapping and repeat SNB in 29 Dutch hospitals. A repeat sentinel node (SN) was identified in 333 of 536 patients (62.1 %) and surgically harvested in 287 patients (53.5 %). Aberrant lymph drainage was observed in 180 (54.1 %) of the 333 patients, more often after previous ALND (81.9 %) than SNB (28.4 %; P < 0.001). In 230 patients (80.1 %), the retrieved SN was tumor negative; 17 SNs (5.9 %) contained a micrometastasis and 29 (10.1 %) a macrometastasis. Confirmation ALND in 31 repeat SN-negative patients revealed a macrometastasis in two patients (6.5 %). The negative predictive value (NPV) of repeat SNB was 93.6 %, and ALND was omitted in 109 of the 248 patients (44.0 %) with a negative repeat SN. In 29 of the 44 patients (63.0 %) with a positive SN, adjuvant treatment plans were altered based on the repeat SNB. Repeat SNB is a feasible procedure with a high NPV, leading to a change in management in a substantial proportion of patients. Therefore, repeat SNB should replace routine ALND and serve as the standard of care in recurrent breast cancer.
Asunto(s)
Neoplasias de la Mama/diagnóstico , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela , Adulto , Anciano , Anciano de 80 o más Años , Axila , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Evaluación del Resultado de la Atención al Paciente , PronósticoRESUMEN
PURPOSE: Repeat sentinel node biopsy (SNB) is an alternative to axillary lymph node dissection (ALND) for axillary staging in recurrent breast cancer. This study was conducted to determine factors associated with technical success of repeat SNB. METHODS: A total of 536 patients with locally recurrent nonmetastatic breast cancer underwent lymphatic mapping (LM) and repeat SNB in 29 Dutch hospitals. RESULTS: A total of 179 patients previously underwent breast-conserving surgery (BCS) with SNB, 262 patients BCS with ALND and 61 patients mastectomy, 35 with SNB and 26 with ALND. Another 34 patients underwent breast surgery without axillary interventions. A repeat sentinel node (SN) was identified in 333 patients (62.1 %) and was successfully removed in 235 (53.5 %). The overall repeat SN identification rate was 62.1 %, varying from 35 to 100 % in the participating hospitals. Previous radiotherapy of the breast [odds ratio (OR) 0.16; 95 % confidence interval (CI) 0.03-0.84], subareolar tracer injection (OR 0.34; 95 % CI 0.16-0.73), and a 2-day LM protocol (OR 0.57; 95 % CI 0.33-0.97) after previous BCS were independently associated with failure of SN identification. Injection of a larger amount of tracer (>180 MBq) led to a higher identification rate (OR 4.40; 95 % CI 1.45-13.32). CONCLUSIONS: Repeat SNB is a technically feasible procedure for axillary staging in recurrent breast cancer patients. Previous radiotherapy appears to be associated with failure of SN identification. Injection with a larger amount of tracer (>180 MBq) leads to a higher identification rate; subareolar injection and a 2-day LM protocol after previous BCS appear to be less adequate.
Asunto(s)
Neoplasias de la Mama/cirugía , Carcinoma Intraductal no Infiltrante/cirugía , Ganglios Linfáticos/cirugía , Recurrencia Local de Neoplasia/cirugía , Biopsia del Ganglio Linfático Centinela , Adulto , Anciano , Anciano de 80 o más Años , Axila , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Mastectomía , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: The purpose of this study was to analyse retrospectively the pooled results after pelvic exenteration for locally advanced T4 rectal cancer. Historically, patients with T4 rectal cancers requiring pelvic exenteration have been offered only palliative surgery or no operation. METHODS: The basic treatment principle was preoperative (chemo)radiotherapy, radical surgery and, in some patients, adjuvant chemotherapy. Risk factors for local recurrence, distant metastases and overall survival were studied in univariable and multivariable analyses. RESULTS: Ninety-five patients with T4 rectal cancer who underwent pelvic exenteration in two tertiary referral centres up to 2013 were studied. Clear margins (R0) were achieved in 87 per cent of patients. Adjuvant chemotherapy was administered in 33 per cent, independent of the resection margin, lymph node status and postoperative T category. The 5-year local recurrence rate was 17 per cent, with a distant metastasis rate of 16 per cent and overall survival rate of 62 per cent. In multivariable analysis the only factor associated with death was omission of adjuvant chemotherapy (P = 0.016). The effect of adjuvant chemotherapy was more pronounced in the elderly: patients aged over 70 years who had chemotherapy had a 5-year overall survival rate of 80 per cent, compared with 39 per cent of elderly patients who did not receive chemotherapy (P = 0.019). CONCLUSION: Pelvic exenteration led to an R0 resection rate of 87 per cent for T4 rectal cancer, giving good local control and overall survival comparable to population-based colorectal cancer survival rates. Adjuvant chemotherapy may improve overall survival further, even in the elderly.
Asunto(s)
Recurrencia Local de Neoplasia/terapia , Exenteración Pélvica/mortalidad , Neoplasias del Recto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Atención Perioperativa/mortalidad , Radioterapia Adyuvante/mortalidad , Neoplasias del Recto/mortalidad , Análisis de SupervivenciaRESUMEN
BACKGROUND: Many developments in medicine are likely to have influenced the treatment of gastrointestinal cancer, including rates of resection. This study sought to investigate changes in surgical resection rates over time among patients with gastrointestinal cancer. METHODS: Patients diagnosed between 1995 and 2012 in the Eindhoven Cancer Registry area were included. Multivariable logistic regression analysis was used to determine the independent influence of interval of diagnosis on the likelihood of having a resection. RESULTS: Among 43,370 patients, crude resection rates decreased between 1995 and 2012 for gastric, colonic and rectal cancer, most notably for patients aged at least 85 years with gastric cancer (from 37.3 to 13.3 per cent), and patients aged 75-84 years and 85 years or more with rectal cancer (from 80.5 to 64.4 per cent, and from 58.9 to 36.0 per cent respectively). After adjustment for patient and tumour characteristics, patients diagnosed between 2008 and 2012 with gastric (odds ratio (OR) 0.71, 95 per cent c.i. 0.55 to 0.92), colonic (OR 0.52, 0.44 to 0.62), rectal (OR 0.39, 0.33 to 0.48) and periampullary (OR 0.42, 0.27 to 0.66) cancers were less likely to undergo resection than those diagnosed between 1995 and 1998. Patients diagnosed with pancreatic cancer were more likely to undergo resection in recent periods (OR 4.13, 2.57 to 6.64). CONCLUSION: Resection rates have fallen over time for several gastrointestinal cancers. This might reflect increased availability of other treatments, better selection of patients as a result of improved diagnostic accuracy, risk-avoiding behaviour and transparency related to surgical outcomes at hospital and surgeon level.