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PURPOSE: No biomarker capable of improving selection and monitoring of patients with rectal cancer managed by watch-and-wait (W&W) strategy is currently available. Prognostic performance of the Immunoscore biopsy (ISB) was recently suggested in a preliminary study. METHODS: This international validation study included 249 patients with clinical complete response (cCR) managed by W&W strategy. Intratumoral CD3+ and CD8+ T cells were quantified on pretreatment rectal biopsies by digital pathology and converted to ISB. The primary end point was time to recurrence (TTR; the time from the end of neoadjuvant treatment to the date of local regrowth or distant metastasis). Associations between ISB and outcomes were analyzed by stratified Cox regression adjusted for confounders. Immune status of tumor-draining lymph nodes (n = 161) of 17 additional patients treated by neoadjuvant chemoradiotherapy and surgery was investigated by 3'RNA-Seq and immunofluorescence. RESULTS: Recurrence-free rates at 5 years were 91.3% (82.4%-100.0%), 62.5% (53.2%-73.3%), and 53.1% (42.4%-66.5%) with ISB High, ISB Intermediate, and ISB Low, respectively (hazard ratio [HR; Low v High], 6.51; 95% CI, 1.99 to 21.28; log-rank P = .0004). ISB was also significantly associated with disease-free survival (log-rank P = .0002), and predicted both local regrowth and distant metastasis. In multivariate analysis, ISB was independent of patient age, sex, tumor location, cT stage (T, primary tumor; c, clinical), cN stage (N, regional lymph node; c, clinical), and was the strongest predictor for TTR (HR [ISB High v Low], 6.93; 95% CI, 2.08 to 23.15; P = .0017). The addition of ISB to a clinical-based model significantly improved the prediction of recurrence. Finally, B-cell proliferation and memory in draining lymph nodes was evidenced in the draining lymph nodes of patients with cCR. CONCLUSION: The ISB is validated as a biomarker to predict both local regrowth and distant metastasis, with a gradual scaling of the risk of pejorative outcome.
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Neoplasias Retais , Conduta Expectante , Humanos , Neoplasias Retais/patologia , Intervalo Livre de Doença , Prognóstico , Quimiorradioterapia , Biópsia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Resultado do TratamentoRESUMO
AIM: Nonsurgical treatment with chemoradiotherapy for rectal cancer is gaining interest as it avoids total mesorectal excision (TME) surgery and stoma. The OPERA trial aims to evaluate whether dose escalation with contact X-ray brachytherapy (CXB) boost improves organ preservation compared to external beam radiotherapy (EBRT) boost. It has been suggested that dose escalation adversely affects surgical outcomes and therefore we report outcomes following TME in OPERA at 36 months. METHODS: OPERA is a European multicentre phase 3 trial (NCT02505750) which randomises patients with cT2-3a-b, cN0-1, M0 to EBCRT (45 Gy in 25 fractions over 5 weeks with oral capecitabine 825 mg/m2 ) followed by EBRT boost (9 Gy in 5 fractions over 5 days) versus EBCRT followed by CXB boost (90 Gy in 3 fractions over 4 weeks). Patients were assessed at 14, 20 and 24 weeks from the start of treatment. Watch and wait management was adopted for patients who achieved a clinical complete response (cCR) at 24 weeks following treatment. Either local excision (LE) or TME surgery was offered for residual disease or local regrowth, according to patient and surgeon preference. Surgical morbidity and mortality were recorded prospectively. RESULTS: Between July 2015 and June 2020, 148 patients were randomised of which 141 were evaluable in March 2022. At median follow-up of 38.2 months (range: 34.2-42.5), surgery was performed for 66 (47%) patients. A total of 27 (20%) patients had local excision and 39 (29%) had TME surgery, 22/39 (56%) underwent anterior resection and 17/39 (44%) underwent abdominoperineal excision of the rectum. The R0 resection rate was 87%. There were no deaths, and six patients (15%) had Clavien-Dindo IIIb complications. Whilst there was a statistically significant decrease in the TME rate following CXB boost (HR 0.38, 95% CI: 0.19-0.74, p = 0.00419) there was no difference in surgical outcomes between patients who received EBRT and CXB boost. CONCLUSION: Dose escalation can facilitate nonsurgical treatment for cT2-3 rectal cancer patients who are fit but wish to avoid TME surgery and stoma. If TME surgery is required, then it can be performed safely and effectively.
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Adenocarcinoma , Neoplasias Retais , Humanos , Preservação de Órgãos , Terapia Neoadjuvante , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Quimiorradioterapia , Resultado do Tratamento , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Recidiva Local de NeoplasiaRESUMO
LARC is managed by multimodal treatments whose intensity can be highly modulated. In this context, we need surrogate endpoints to help predict long-term outcomes and better personalize treatments. A previous study identified 2yDFS as a stronger predictor of OS than pCR in LARC patients undergoing neoadjuvant RT. The aim of this pooled analysis was to assess the role of pCR and 2yDFS as surrogate endpoints for OS in a larger cohort. The pooled and subgroup analyses were performed on large rectal cancer randomized trial cohorts who received long-course RT. Our analysis focused on the evaluation of OS in relation to the pCR and 2-year disease status. A total of 4600 patients were analyzed. Four groups were identified according to intermediate outcomes: 12% had both pCR and 2yDFS (the better); 67% achieved 2yDFS but not pCR (the good); 1% had pCR but not 2yDFS; and 20% had neither pCR nor 2yDFS (the bad). The pCR and 2yDFS were favorably associated with OS in the univariate analysis, and 2yDFS maintained a statistically significant association in the multivariate analysis independently of the pCR status. The combination of the pCR and 2yDFS results in a strong predictor of OS, whereas failure to achieve 2yDFS carries a poor prognosis regardless of the pCR status. This new stratification of LARC patients could help design predictive models where the combination of 2yDFS and pCR should be employed as the primary outcome.
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PURPOSE: To develop guidelines by international experts to standardize data acquisition, image interpretation, and reporting in rectal cancer restaging with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Evidence-based data and experts' opinions were combined using the RAND-UCLA Appropriateness Method to attain consensus guidelines. Experts provided recommendations for reporting template and protocol for data acquisition were collected; responses were analysed and classified as "RECOMMENDED" versus "NOT RECOMMENDED" (if ≥ 80% consensus among experts) or uncertain (if < 80% consensus among experts). RESULTS: Consensus regarding patient preparation, MRI sequences, staging and reporting was attained using the RAND-UCLA Appropriateness Method. A consensus was reached for each reporting template item among the experts. Tailored MRI protocol and standardized report were proposed. CONCLUSION: These consensus recommendations should be used as a guide for rectal cancer restaging with MRI.
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Canal Anal , Neoplasias Retais , Humanos , Estadiamento de Neoplasias , Imageamento por Ressonância Magnética/métodos , Neoplasias Retais/diagnóstico por imagem , Consenso , Terapia NeoadjuvanteRESUMO
BACKGROUND: Organ preservation after reaching clinical complete response on neoadjuvant therapy is gaining interest for rectal cancers, although the role of radiation dose escalation is still not known. We aimed to determine whether a contact x-ray brachytherapy boost, following or preceding neoadjuvant chemoradiotherapy, increases the probability of 3-year organ preservation for patients with early rectal cancers. METHODS: OPERA was a multicentre, open-label, phase 3 randomised controlled trial done at 17 cancer centres that included operable patients, aged 18 years or older, with cT2, cT3a, or cT3b adenocarcinoma of low-mid rectum, tumours of less than 5 cm in diameter, and cN0 or cN1 smaller than 8 mm. All patients received neoadjuvant chemoradiotherapy and 45 Gy external beam radiotherapy in 25 fractions over 5 weeks with concurrent oral capecitabine (825 mg/m2 twice a day). Patients were randomly assigned (1:1) to receive a boost of external beam radiotherapy at 9 Gy in five fractions (group A) or a boost with contact x-ray brachytherapy (90 Gy in three fractions; group B). Randomisation was done centrally using an independent web-based system and stratified by trial centre, tumour classification (cT2 vs cT3a or cT3b), tumour distance from rectum (<6 cm from anal verge vs ≥6 cm), and tumour diameter (<3 cm vs ≥3 cm). Treatment in group B was stratified by tumour diameter, with the contact x-ray brachytherapy boost given before neoadjuvant chemoradiotherapy in patients with tumours smaller than 3 cm. The primary outcome was organ preservation at 3 years, analysed in the modified intention-to-treat population. This study was registered with ClinicalTrials.gov, NCT02505750, and is ongoing. FINDINGS: Between June 14, 2015, and June 26, 2020, 148 patients were assessed for eligibility and were randomly assigned to group A (n=74) or group B (n=74). Seven patients withdrew their consent (five in group A and two in group B). 141 patients were included in the primary efficacy analysis, including 69 assigned to group A (29 with tumours <3 cm in diameter and 40 with tumours ≥3 cm) and 72 assigned to group B (32 with tumours <3 cm and 40 with tumours ≥3 cm). After a median follow-up of 38·2 months (IQR 34·2-42·5), the 3-year organ preservation rate was 59% (95% CI 48-72) in group A versus 81% (72-91) in group B (hazard ratio [HR] 0·36, 95% CI 0·19-0·70; p=0·0026). For patients with tumours less than 3 cm in diameter, 3-year organ preservation rates were 63% (95% CI 47-84) in group A versus 97% (91-100) in group B (HR 0·07, 95% CI 0·01-0·57; p=0·012). For patients with tumours of 3 cm or larger, 3-year organ preservation rates were 55% (95% CI 41-74) in group A versus 68% (54-85) in group B (HR 0·54, 95% CI 0·26-1·10; p=0·11). 21 (30%) patients in group A and 30 (42%) in group B had an early grade 2-3 adverse event (p=1·0). The most common early grade 2-3 adverse events were proctitis (four [6%] in group A, nine [13%] in group B) and radiation dermatitis (seven [10%] in group A, two [3%] in group B). The main late side-effect was grade 1-2 rectal bleeding due to telangiectasia, which was more frequent in group B (37 [63%] of 59) than in group A (five [12%] of 43; p<0·0001) and subsided after 3 years. INTERPRETATION: Neoadjuvant chemoradiotherapy with a contact x-ray brachytherapy boost significantly improved the 3-year organ preservation rate, particularly for patients with tumours smaller than 3 cm who were treated with contact x-ray brachytherapy first, compared with neoadjuvant chemoradiotherapy with a boost via external beam radiotherapy. This approach could be discussed and offered to operable patients with early cT2-cT3 disease who are keen to avoid surgery and seek organ preservation. FUNDING: The French Programme Hospitalier de Recherche Cinique.
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Adenocarcinoma , Braquiterapia , Neoplasias Retais , Humanos , Terapia Neoadjuvante , Raios X , Preservação de Órgãos , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Adenocarcinoma/patologia , Doses de RadiaçãoRESUMO
Background and Purpose: Breast intra operative radiation therapy has been evaluated with different systems delivering 20-21 Gy with treatment times around 30 min. Papillon + TM Contact X-ray machine was designed to produce a 50 kVp beam with a high dose rate ≥ 15 Gy/minute. A pilot study with the first prototype was conducted in Nice. Materials and methods: The inclusion criteria were age ≥ 60 years, unifocal ductal breast adenocarcinoma ≤ 2.5 cm, grade 1-2. Surgical local excision with sentinel node dissection was performed and the applicator was placed in the tumor bed after excision with a prescribed dose of 20 Gy. The main end point of the study was the doses measured with the Gafchromic films; two were located at the skin surface and two in the excision cavity. Secondary endpoints were early toxicity and relapse free survival. Results: Between 10/2018 and 09/2019, 26 patients were included. Mean Gafchromic doses were 18.8 Gy ± 2 Gy at the south pole, 15.6 Gy ± 2.81 Gy at the equator and 2.5 Gy ± 1.67 Gy at the skin. With a median follow-up time of 12 months, no skin or subcutaneous toxicity > grade 2, no local relapse and no metastasis were observed. Conclusion: This is the first phase II study testing the Papillon + tm system for breast IORT with in vivo dosimetry measurements and reassuring clinical data.
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BACKGROUND: The impact of the tumour volume or size on achieving clinical complete response (cCR) after radio(chemo)therapy is poorly understood. MATERIALS AND METHODS: A literature search was performed to gather data on the predictive value of baseline tumour volume or size in achieving cCR. RESULTS: In total, nine reports were identified. In two of three studies evaluating the baseline tumour volumetry, the tumour volume was the most powerful predictor for cCR. In four of six studies evaluating baseline tumour size without volumetry, tumour dimension was significantly associated with cCR, in one study reached borderline significance and in one report was insignificant. In three of four studies where a multivariable analysis was performed, the cT category did not show an independent predictive value for cCR. Because the tumour shape is often (semi)annular, its circumferential rectal extent along with the tumour length probably impact the tumour volume most, and thus, could be considered an acceptable alternative for time-consuming volumetry. CONCLUSIONS: Our review suggests that baseline tumour volume (or alternatively, tumour length along with its circumferential rectal extent) is the most relevant clinical predictor of cCR. Therefore, we postulate assessing and reporting these parameters in studies on the watch-and-wait strategy.
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Terapia Neoadjuvante , Neoplasias Retais , Humanos , Carga Tumoral , Conduta Expectante , Recidiva Local de Neoplasia , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Margens de Excisão , Quimiorradioterapia , Resultado do TratamentoRESUMO
Background and Purpose: Tumor recurrence, a characteristic of malignant tumors, is the biggest concern for rectal cancer survivors. The epidemiology of the disease calls for a pressing need to improve healthcare quality and patient outcomes. Prediction models such as Bayesian networks, which can probabilistically reason under uncertainty, could assist caregivers with patient management. However, some concerns are associated with the standard approaches to developing these structures in medicine. Therefore, this study aims to compare Bayesian network structures that stem from these two techniques. Patients and Methods: A retrospective analysis was performed on 6754 locally advanced rectal cancer (LARC) patients enrolled in 14 international clinical trials. Local tumor recurrence at 2, 3, and 5-years was defined as the endpoints of interest. Five rectal cancer treating physicians from three countries elicited the expert structure. The algorithmic structure was inferred from the data with the hill-climbing algorithm. Structural performance was assessed with calibration plots and area under the curve values. Results: The area under the curve for the expert structure on the training and validation data was above 0.9 and 0.8, respectively, for all the time points. However, the algorithmic structure had superior predictive performance over the expert structure for all time points of interest. Conclusion: We have developed and internally validated a Bayesian networks structure from experts' opinions, which can predict the risk of a LARC patient developing a tumor recurrence at 2, 3, and 5 years. Our result shows that the algorithmic-based structures are more performant and less interpretable than expert-based structures.
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PURPOSE: To issue consensus recommendations for contact X-Ray brachytherapy (CXB) for rectal cancer covering pre-treatment evaluation, treatment, dosimetric issues and follow-up. These recommendations cover CXB in the definitive and palliative setting. METHODS: Members of GEC ESTRO with expertise in rectal CXB issued consensus-based recommendations for CXB based on literature review and clinical experience. Levels of evidence according to the Oxford Centre for Evidence based medicine guidance are presented where possible. RESULTS: The GEC ESTRO ACROP consensus recommendations support the use of CXB to increase the chances of clinical complete remission and cure for patients who are elderly with high surgical risk, surgically unfit or refusing surgery. For palliative treatment, the use of CXB is recommended for symptomatic relief and disease control. The use of CXB in an organ-preservation setting in surgically fit patients is recommended within the setting of a clinical trial or registry. CONCLUSIONS: The GEC ESTRO ACROP recommendations for CXB are provided. Recommendations towards standardisation of reporting and prescription are given. Practitioners are encouraged to follow these recommendations and to develop further clinical trials to examine this treatment modality and increase the evidence base for its use. The routine collection of outcomes both clinical and patient-reported is also encouraged.
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Rectal adenocarcinoma is a quite radioresistant tumor. In order to achieve non-operative management (NOM) radiotherapy plays a major role. Targeted radiotherapy aiming at high precision 3D radiotherapy uses stereotactic image-guided external beam radiotherapy machines. To further safely increase the tumor dose, endocavitary brachytherapy (ECB) is an original approach. There are two different ways to perform such an ECB: contact X-ray brachytherapy (CXB) using a 50 kV X-ray generator with an X-ray tube positioned under eye guidance into the rectal cavity and high-dose-rate brachytherapy (HDRB) using iridium-192 sources positioned into the rectal cavity under image guidance. This study focused on CXB. CXB uses a small mobile generator that produces 50 kV X-rays with limited penetration. This technique is well adapted to accessible tumors of limited size and especially needs a high dose rate (≥15 Gy/minutes) for rectal tumors. It is performed on an ambulatory basis. A total dose between 80−110 Gy is delivered in 3−4 fractions over 3 to 6 weeks into a small volume (5 cm3). CXB was pioneered in the 1970s by Papillon using the Philips RT 50TM. Since 2009, the Papillon P50TM has been used in 11 institutions in Europe. The OPERA Phase III trial tested the hypothesis that a CXB boost (90 Gy/3 fr) compared to an EBRT boost (9 Gy/5 fr) for T2−T3 ab < 5 cm and N0−N1 < 8 mm will increase the 3-year organ preservation (OP) rate when combined with 45 Gy/5 weeks with concomitant capecitabine. Out of more than 300 patients with tumors < 3 cm (1962−1992), Papillon reported a long-term local control close to 85%. Similar results were published in Europe and USA at that time. The Lyon R96-2 Phase III trial (2004) demonstrated that, when combined with preoperative EBRT, a CXB boost (90 Gy/3 fr) significantly increased the rate of clinical complete response (cCR) and sphincter preservation, with some patients having OP at 10 years. With more than 2000 patients treated in Europe (2010−2020) using the Papillon 50TM, organ preservation appears possible in close to 80% of cases in selected early T2−T3. The OPERA trial closed after 141 inclusions (2015−2020) after an independent data monitoring committee recommendation because of promising results. At the 2-year follow-up (blinded data), the rate of cCR and OP were 77% and 72%, respectively, for the 141 tumors, and for T < 3 cm (61 pts), they were 86% and 85%, respectively, with good bowel function. The final results should be available in 2022. Organ preservation using NOM appears to be a promising approach for rectal cancer. A CXB boost with chemoradiotherapy in selected early T2−T3 could become an attractive option to achieve a planned OP. This approach should be proposed to well-informed patients after discussion in an MDT.
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INTRODUCTION: Radical proctectomy (RP-TME) with neo adjuvant chemoradiotherapy (nCRT) remains the standard treatment for T2-T3 rectal cancer. Organ preservation (OP) using CRT and a "watch and wait" strategy (W&W) is a field of research. Planned organ preservation can be proposed for early T1-T3 using contact X-ray brachytherapy (CXB). We compared the oncological outcomes of both approaches using a propensity score matched-cohort analysis. MATERIAL AND METHODS: For comparative analyses between patients with nCRT + RP-TME and patients with CXB + CRT, propensity scores were calculated with logistic regression and multiple imputations for missing data. The variables included in the propensity score model were PS status, T-N stage and rectal circumference extension. Patients were matched 1:1 using the nearest neighbor method with a 0.1 caliper restriction. The 5-year Cancer Specific survival was the primary end point. RESULTS: The Accord 12 phase III trial included 584 patients who treated with nCRT + RP-TME. The CXB cohort included 71 patients with a planned OP. To select OP patient candidate, T4, tumor with extension >66% circumference were eliminated and only patients treated with CXB + CRT were analyzed in the CXB cohort resulting in a total of 374 patients. A one to one paired cohort with 36 patients in each group was derived. These two cohorts were well matched for all confounding factors except for age. The 5-year cancer specific rate showed no significant difference between the two groups (89% in Accord 12 vs 82% in CXB; p = 0.84). At 5 years, rate of metastasis (15% vs 22%, p = 0.54) showed no significant difference. In the CXB group 33/36 patients preserved their rectum. CONCLUSION: The organ preservation strategy using CXB boost yielded a 5-year cancer specific survival rate similar to patients treated with RP-TME. In selected early T2-3 rectal adenocarcinoma an organ preservation strategy could be offered as a reasonable option.
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Because of the function and anatomical environment of the rectum, therapeutic strategies for local advanced rectal cancer (LARC) must deal with two challenging stressors that are a high-risk of local and distal recurrences and a high-risk of poor quality of life (QoL). Over the last three decades, advances in screening tests, therapies, and combined-modality treatment options and strategies have improved the prognosis of patients with LARC. However, owing to the heterogeneous nature of LARC and genetic status, the patient may not respond to a specific therapy and may be at increased risk of side-effects without the life-prolonging benefit. Indeed, each therapy can cause its own side-effects, which may worsen by a combination of treatments resulting in long-term poor QoL. In LARC, QoL has become even more essential with the increasing incidence of rectal cancer in young individuals. Herein, we analyzed the value of the Immunoscore-Biopsy (performed on tumor biopsy at diagnosis) in predicting outcomes, alone or in association with clinical and imaging data, for each therapy used in LARC.
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Qualidade de Vida , Neoplasias Retais , Quimiorradioterapia/métodos , Humanos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/patologia , Prognóstico , Neoplasias Retais/patologia , Reto/patologia , Resultado do TratamentoRESUMO
PURPOSE: To develop French guidelines by experts to standardize data acquisition, image interpretation, and reporting in rectal cancer staging with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Evidence-based data and opinions of experts of GRERCAR (Groupe de REcherche en Radiologie sur le CAncer du Rectum [i.e., Rectal Cancer Imaging Research Group]) and GRECCAR (Groupe de REcherche en Chirurgie sur le CAncer du Rectum [i.e., Rectal Cancer Surgery Research Group]) were combined using the RAND-UCLA Appropriateness Method to attain consensus guidelines. Experts scoring of reporting template and protocol for data acquisition were collected; responses were analyzed and classified as "Recommended" versus "Not recommended" (when ≥ 80% consensus among experts) or uncertain (when < 80% consensus among experts). RESULTS: Consensus regarding patient preparation, MRI sequences, staging and reporting was attained using the RAND-UCLA Appropriateness Method. A consensus was reached for each reporting template item among the experts. Tailored MRI protocol and standardized report were proposed. CONCLUSION: These consensus recommendations should be used as a guide for rectal cancer staging with MRI.
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Radiologia , Neoplasias Retais , Consenso , Humanos , Imageamento por Ressonância Magnética/métodos , Estadiamento de Neoplasias , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologiaRESUMO
Multimodal treatment strategies for patients with rectal cancer are increasingly including the possibility of organ preservation, through nonoperative management or local excision. Organ preservation strategies can enable patients with a complete response or near-complete clinical responses after radiotherapy with or without concomitant chemotherapy to safely avoid the morbidities associated with radical surgery, and thus to maintain anorectal function and quality of life. However, standardization of the key outcome measures of organ preservation strategies is currently lacking; this includes a lack of consensus of the optimal definitions and selection of primary end points according to the trial phase and design; the optimal time points for response assessment; response-based decision-making; follow-up schedules; use of specific anorectal function tests; and quality of life and patient-reported outcomes. Thus, a consensus statement on outcome measures is necessary to ensure consistency and facilitate more accurate comparisons of data from ongoing and future trials. Here, we have convened an international group of experts with extensive experience in the management of patients with rectal cancer, including organ preservation approaches, and used a Delphi process to establish the first international consensus recommendations for key outcome measures of organ preservation, in an attempt to standardize the reporting of data from both trials and routine practice in this emerging area.
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Preservação de Órgãos/normas , Neoplasias Retais/terapia , Quimiorradioterapia/efeitos adversos , Consenso , Técnica Delphi , HumanosRESUMO
INTRODUCTION: Early rectal cancers are increasingly diagnosed through screening programmes and are often treated using local excision (LE). In the case of adverse pathological features completion total mesorectal excision surgery (TME) is the standard recommendation. The morbidity and mortality risks of TME have stimulated the use of adjunctive treatments following LE to achieve organ preservation. MATERIAL AND METHODS: Patients treated with adjuvant CXB following local excision between 2004 and 2017 in three centres were identified (Clatterbridge, Hull, Nice). All patients had adverse pathological features including: lymphovacular invasion, Sm2-3 Kikuchi level, tumour budding, pT2, positive resection margins (R1). CXB was performed with the Papillon50 tm machine to a dose of 40-60 Gy in 2 or 3 fractions over 2-4 weeks preceding/following external beam chemo/radiotherapy. Kaplan Meier survival estimates were used for outcomes measures. RESULTS: 194 patients were identified. Median age was 70 years. pT staging was: pT1:143, pT2:45, pT3:6. CXB alone was given in 24 pts and combined with EBRT in 170. Median follow-up time was 77 months (range 7-122 months). Local relapse rate was 8% and distant metastases 9%. Organ preservation was achieved in 95%. 6 year local recurrence free and overall survival was 91% and 81% respectively. Cancer specific survival was 97%. No treatment related mortality was seen. CONCLUSION: This large multi-centre cohort study using adjuvant CXB following local excision suggests excellent oncological outcomes for these patients without completion TME. This treatment approach can be considered as an alternative for selective patients compliant with long term follow up.
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Braquiterapia , Neoplasias Retais , Idoso , Estudos de Coortes , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Resultado do Tratamento , Raios XRESUMO
BACKGROUND: Little is known about the management of squamous cell carcinoma of the anal canal and its recurrence at a population level. The aim of this study was to draw a picture of management, recurrence and survival in squamous cell carcinoma of the anal canal. MATERIAL AND METHODS: The 5-year probability of recurrences was estimated using the cumulative incidence function to consider competing risks of death. Net survival was estimated and a multivariate survival analysis was performed. The study was conducted using data of the Burgundy Digestive Cancer Registry. Overall, 273 squamous cell carcinomas of the anal canal registered between 1998 and 2014 were considered. RESULTS: Overall, 80% of patients were treated with curative intent. Of these, 61% received chemoradiotherapy, 35% received radiotherapy and 4% received abdominoperineal resection alone. After these treatments, for cure the 5-year cumulative recurrence rate was 27% overall; it was 20% after chemoradiotherapy and 38% after radiotherapy. Five-year net survival was 71% overall; it was 81% after chemoradiotherapy and 55% after radiotherapy. CONCLUSIONS AND RELEVANCE: Chemoradiotherapy was highly effective in routine practice. We confirm that it is difficult to distinguish between persistent active disease and local inflammation due to radiotherapy. Squamous cell carcinoma of the anal canal recurrences remains a substantial problem, highlighting the interest of prolonged surveillance. Aggressive management of recurrences may be beneficial.
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Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/estatística & dados numéricos , Recidiva Local de Neoplasia/terapia , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/mortalidade , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Resultado do TratamentoRESUMO
PURPOSE: Optimal timing of surgery after neoadjuvant chemoradiotherapy (Nad-CRT) is still controversial in locally advanced rectal cancer (LARC). The primary goal of this study was to determine the best surgical interval (SI) to achieve the highest rate of pathological complete response (pCR) and secondly to evaluate the effect on survival outcomes according to the SI. PATIENTS AND METHODS: Patients data were extracted from the international randomized trials: Accord12/0405, EORTC22921, FFCD9203, CAO/ARO/AIO-94, CAO-ARO-AIO-04, INTERACT and TROG01.04. Inclusion criteria were: age≥ 18, cT3-T4 and cN0-2, no clinical evidence of distant metastasis at diagnosis, Nad-CRT followed by surgery. Pearson's Chi-squared test with Yates' continuity correction for categorical variables, the Mann-Whitney test for continuous variables, Mann-Kendall test, Kaplan-Meier curves with log-rank test, univariate and multivariate logistic regression model was used for data analysis. RESULTS: 3085 patients met the inclusion criteria. Overall, the pCR rate was 14% at a median SI of 6 weeks (range 1-31). The cumulative pCR rate increased significantly when SI lengthened, with 95% of pCR events within 10 weeks from Nad-CRT. At univariate and multivariate logistic regression analysis, lengthening of SI (p< 0.01), radiotherapy dose (p< 0.01), and the addition of oxaliplatin to Nad-CRT (p< 0.01) had a favorable impact on pCR. Furthermore, lengthening of SI was not impact on local recurrences, distance metastases, and overall survival. CONCLUSION: This pooled analysis suggests that the best time to achieve pCR in LARC is at 10 weeks, considering that the lengthening of SI is not detrimental concerning survival outcomes.
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Recidiva Local de Neoplasia , Neoplasias Retais , Adolescente , Quimiorradioterapia , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Retais/patologia , Resultado do TratamentoRESUMO
INTRODUCTION: A neoadjuvant treatment aimed at rectal preservation should achieve a clinical complete response. This study comparing neoadjuvant treatment initiated with Contact X-ray (CXB) or External Beam radiotherapy (EBRT) is evaluating the influence of the time/dose parameter on clinical response during the first six months. MATERIALS AND METHODS: This retrospective consecutive series included T2-3 rectal adenocarcinoma staged using digital examination (DRE), endoscopy, magnetic radiation imaging and/or endorectal ultrasound. All patients were treated with organ preservation intent. Treatment protocol combined CXB (80-110 Gy/3-4 fractions) and EBRT ± concurrent capecitabine. In tumor exceeding 3.5 cm treatment was often initiated using EBRT. Clinical response was assessed (DRE, proctoscopy ± imaging) at very close interval between 2 weeks and 6 months after treatment initiation. RESULTS: Between 2002 and 2017, 61 patients (T2: 31; T3: 30) M0 (median age: 76 years) were treated. Treatment was initiated in 40 patients (T2: 28, T3: 12) with contact X-ray and in 21 (T2: 4, T3: 17) with EBRT. Using contact X-ray or EBRT first treatment, clinical complete (or near complete) response at week 14(±1) was respectively 88% [95CI:74-96] and 33% [95CI:15-57]. In multivariate analysis the treatment chronology was the most significant factor influencing cCR (OR: 7.53). At 6 months, with contact X-ray first all patients were in clinical complete response and five with EBRT remained in partial response. With 61 months median follow-up time, the local recurrence rate was 10% [95% CI: 6-16] at 5 years. T3 and fungating tumors were at higher risk of local recurrence. Organ preservation with good function was achieved in 95% of cases. CONCLUSION: This non randomized study tends to show that in early T2-3 tumors, a strategy using upfront contact therapy, which is reducing the overall treatment time, is an option allowing a more favorable outcome than EBRT first.
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PURPOSE: No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (ISB) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy ("Watch-and-Wait"). EXPERIMENTAL DESIGN: Biopsies from two independent cohorts (n 1 = 131, n 2 = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3+ and CD8+ T cells and quantified by digital pathology to determine ISB. The expression of immune-related genes post-nT was investigated (n = 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The ISB prognostic performance was further assessed in a multicentric cohort (n = 73 patients) treated by Watch-and-Wait. RESULTS: ISB positively correlated with the degree of histologic response (P < 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT (P = 0.006). ISB high identified patients at lower risk of relapse or death compared with ISB low [HR, 0.21; 95% confidence interval (CI), 0.06-0.78; P = 0.009]. Prognostic performance of ISB for DFS was confirmed in a validation cohort. ISB was an independent parameter, more informative than pre- (P < 0.001) and post-nT (P < 0.05) imaging to predict DFS. ISB combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the "Watch-and-Wait" cohort (n = 73), no relapse was observed in patients with ISB high (23.3%). CONCLUSIONS: ISB predicts response to nT and survival in patients with LARC treated by surgery. Its usefulness in the selection of patients eligible for a Watch-and-Wait strategy is strongly suggested.