Bifractionated CPT-11 with LV5FU2 infusion (FOLFIRI-3) in combination with bevacizumab: clinical outcomes in first-line metastatic colorectal cancers according to plasma angiopoietin-2 levels.

International audienceBACKGROUND: Optimization of chemotherapy effectiveness in metastatic colorectal cancers (mCRC) is a major endpoint to enhance the possibility of curative intent surgery. FOLFIRI3 has shown promising results as second-line chemotherapy for mCRC patients previously exposed to oxaliplatin. The clinical efficacy of FOLFIRI3 was never determined in association with bevacizumab in non-previously treated mCRC patients. METHODS: We conducted a phase II clinical trial to characterize the response rate and toxicity profile of FOLFIRI3-bevacizumab as initial treatment for mCRC. Sixty-one patients enrolled in 3 investigation centers were treated with FOLFIRI3-bevacizumab (median of 10 cycles) followed by a maintenance therapy combining bevacizumab and capecitabine. Levels of plasma angiopoietin-2 (Ang-2) were measured by enzyme-linked immunosorbent assay at baseline. RESULTS: Overall response rate (ORR) was 66.7% (8% of complete and 58% of partial responses). The disease control rate was 91.7%. After a median time of follow-up of 46.7 months, 56 patients (92%) had progressed or died. The median progression free survival (PFS) was 12.7 months (95% confidence interval (CI) 9.7-15.8 months). The median overall survival (OS) was 24.5 months (95% CI: 10.6-38.3 months). Twenty-one patients underwent curative intent-surgery including 4 patients with disease initially classified as unresectable. Most common grade III-IV toxicities were diarrhea (15%), neutropenia (13%), asthenia (10%), and infections (4%). Hypertension-related medications needed to be increased in 3 patients. In multivariate analysis, surgery of metastases and Ang-2 levels were the only independent prognostic factors for PFS and OS. Indeed, baseline level of Ang-2 above 5 ng/mL was confirmed as an independent prognostic factor for progression free survival (HR = 0.357; 95% CI: 0.168-0.76, p = 0.005) and overall survival (HR = 0.226; 95% CI: 0.098-0.53, p = 0.0002). CONCLUSIONS: As front-line therapy, FOLFIRI-3-bevacizumab is associated with an acceptable toxicity and induced promising objective response rates. However, unfavorable clinical outcomes were observed in patients with high levels of angiopoietin-2

Bevacizumab Efficacy in Metastatic Colorectal Cancer is Dependent on Primary Tumor Resection

PURPOSE: Bevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and second-line metastatic colorectal cancer (mCRC). However, to date, there is no current biomarker predictive for the benefit of bevacizumab use for these patients. Preclinical data suggest that the presence of the primary tumor could be involved in less efficient antitumor activity of antiangiogenic agents, but no clinical data currently support this hypothesis. METHODS: We performed a retrospective analysis of factors associated with overall survival (OS) in a study cohort of 409 mCRC patients. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of primary tumor resection and bevacizumab use on OS. We evaluated associations linking bevacizumab use and OS among patients who previously underwent or did not undergo primary tumor resection. Results were externally validated in a second independent cohort of 328 mCRC patients. RESULTS: In the study cohort, bevacizumab use and resection of the primary tumor were associated with improved OS. However, subgroup analyses indicate that bevacizumab did not influence survival of patients bearing a primary colorectal tumor (hazard ratio (HR) 0.98, 95 % confidence interval (CI) 0.60–1.61, log-rank test P = 0.6). By contrast, the survival benefit of bevacizumab was restricted to patients who previously underwent primary tumor resection (HR 0.71, 95 % CI 0.55–0.92, P = 0.009). Similar results were observed in the validation cohort. CONCLUSIONS: Addition of bevacizumab to chemotherapy is associated with improvement of OS only in patients with primary tumor resection. These data support the rationale to validate prospectively the influence of primary tumor resection on bevacizumab antitumor effect in synchronous mCRC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1245/s10434-013-3463-y) contains supplementary material, which is available to authorized users

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (<50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, <50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Impact pronostique et thérapeutique du cancer de prostate sur la prise en charge du cancer du rectum

Rectum and prostate are two pelvic organs with intimate anatomical relationships. Previous or synchronous prostate cancer may alter outcomes and management of rectal cancer.Using datas from three multicenter retrospective cohorts, three objectives have been explored. First, assessing the impact of a history of prostate cancer on morbidity and prognosis of resected rectal cancer. Then, assessing safety and morbidity of a strategy with bowel restorative surgery. Finally, describing management and treatment of synchronous rectal and prostate cancer.A history of prostate cancer significantly increased the rate of anastomotic leakage at rectal surgery (25% vs. 14%, p = 0.019) and local recurrence rate (17% vs. 8%, p = 0.019). Then, we did not find any significant increased morbidity when digestive anastomosis was performed (p = 0.08). Delayed coloanal anastomosis might be a safe option. Finally, simultaneous curative management is possible for synchronous prostate and rectal cancers; an algorithm could help decision-making.Management of metachronous or synchronous rectal and prostate cancers is uncommon. Multidisciplinary and specialized decision is paramount.Le rectum et la prostate sont deux organes pelviens aux rapports anatomiques intimes. La survenue préalable ou concomitante d’un cancer de prostate pourrait modifier les résultats et la prise en charge du cancer du rectum.A l’aide de trois cohortes rétrospectives multicentriques, trois objectifs ont été définis. Premièrement, évaluer l’impact d’un antécédent de cancer de prostate sur la morbidité et le pronostic du cancer du rectum opéré. Ensuite, évaluer la morbidité d’une stratégie de rétablissement de continuité digestive. Enfin, étudier la prise en charge et les modalités de traitement cancers du rectum et de prostate synchrones.Un antécédent de cancer de prostate augmentait significativement le taux de fistule anastomotique au cours de la chirurgie rectale (25% vs. 14% ; p=0,019) ainsi que le taux de récidive locale (17% vs. 8% ; p=0,019). Nous n’avons pas retrouvé d’augmentation significative de la morbidité chirurgicale en cas de réalisation d’une anastomose digestive (p=0,08). La réalisation d’une anastomose coloanale différée pourrait être la solution la moins morbide. Enfin, en cas de tumeurs synchrones, nous avons montré qu’une prise en charge à visée curative simultanée était possible pour les deux tumeurs et qu’un algorithme de traitement pourrait aider à la prise de décision.La prise en charge d’un cancer du rectum métachrone ou synchrone d’un cancer de prostate est une situation peu fréquente. Une prise en charge multidisciplinaire et spécialisée est essentielle

Prognostic and therapeutic impact of prostate cancer on rectal cancer management.

Le rectum et la prostate sont deux organes pelviens aux rapports anatomiques intimes. La survenue préalable ou concomitante d’un cancer de prostate pourrait modifier les résultats et la prise en charge du cancer du rectum.A l’aide de trois cohortes rétrospectives multicentriques, trois objectifs ont été définis. Premièrement, évaluer l’impact d’un antécédent de cancer de prostate sur la morbidité et le pronostic du cancer du rectum opéré. Ensuite, évaluer la morbidité d’une stratégie de rétablissement de continuité digestive. Enfin, étudier la prise en charge et les modalités de traitement cancers du rectum et de prostate synchrones.Un antécédent de cancer de prostate augmentait significativement le taux de fistule anastomotique au cours de la chirurgie rectale (25% vs. 14% ; p=0,019) ainsi que le taux de récidive locale (17% vs. 8% ; p=0,019). Nous n’avons pas retrouvé d’augmentation significative de la morbidité chirurgicale en cas de réalisation d’une anastomose digestive (p=0,08). La réalisation d’une anastomose coloanale différée pourrait être la solution la moins morbide. Enfin, en cas de tumeurs synchrones, nous avons montré qu’une prise en charge à visée curative simultanée était possible pour les deux tumeurs et qu’un algorithme de traitement pourrait aider à la prise de décision.La prise en charge d’un cancer du rectum métachrone ou synchrone d’un cancer de prostate est une situation peu fréquente. Une prise en charge multidisciplinaire et spécialisée est essentielle.Rectum and prostate are two pelvic organs with intimate anatomical relationships. Previous or synchronous prostate cancer may alter outcomes and management of rectal cancer.Using datas from three multicenter retrospective cohorts, three objectives have been explored. First, assessing the impact of a history of prostate cancer on morbidity and prognosis of resected rectal cancer. Then, assessing safety and morbidity of a strategy with bowel restorative surgery. Finally, describing management and treatment of synchronous rectal and prostate cancer.A history of prostate cancer significantly increased the rate of anastomotic leakage at rectal surgery (25% vs. 14%, p = 0.019) and local recurrence rate (17% vs. 8%, p = 0.019). Then, we did not find any significant increased morbidity when digestive anastomosis was performed (p = 0.08). Delayed coloanal anastomosis might be a safe option. Finally, simultaneous curative management is possible for synchronous prostate and rectal cancers; an algorithm could help decision-making.Management of metachronous or synchronous rectal and prostate cancers is uncommon. Multidisciplinary and specialized decision is paramount

Is There Any Reason Not to Perform Standard Laparoscopic Total Mesorectal Excision?

AbstractThe curative treatment of locally advanced rectal cancer is currently based on chemoradiotherapy and total mesorectal excision (TME). Laparoscopy has developed considerably because of obvious clinical benefits such as reduced pain and shorter hospital stay. Recently, several prospective randomized clinical trials with long-term follow-up have showed that laparoscopy is noninferior to laparotomy with the same oncologic outcomes in terms of survival and local control rate. However, laparoscopic TME remains a challenging procedure requiring a high level of expertise and a long learning curve to ensure an adequate and safe resection. The only relative contraindication of laparoscopic rectal surgery is T4 rectal cancer extended beyond the plane of TME. In this situation, it is reasonable to consider an open resection to avoid an uncomplete resection. In obese and elderly patients, laparoscopic TME also provides the same benefits as in nonobese and younger patients but may be more difficult to achieve. This review summarizes current knowledge on the place of laparoscopic TME in the treatment of rectal cancer.</jats:p