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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.

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.

Highlights • Treatment initiation of T2-T3 rectal cancers with Contact (CXB) provides a fast clinical complete response. • In T2N0< 3 cm tumors, CXB first with chemoradiotherapy can achieve local control in more than 85%. • The Phase III OPERA trial should bring robust data in favor of CXB as initial treatment of T2N0< 3 cm., 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.

Striking a balance between cancer treatment and patient-centred care is becoming ever more important in older patients with rectal cancer as the population is ageing. The treatment decision made by the modern multidisciplinary colorectal team will recommend pre-operative chemo-radiotherapy followed by surgery for advance rectal cancer and surgery alone for early rectal cancer, as the "standard of care" is surgery. However, an alternative non-surgical treatment option should be consider for older patients with rectal cancer as the surgical harm can far outweigh the potential benefits. There is published evidence that mortality is higher with increasing age. An alternative treatment option to surgery when patients are not suitable or refusing surgery is to offer them external beam radiotherapy (EBRT) or chemo radiotherapy (EBCRT). A proportion of these patients can achieve a clinical complete response (cCR) which enable adoption of 'watch and wait' strategy to avoid surgery. However, a third of patients who achieved initial cCR can develop local regrowth within the first two years. This require salvage surgery which reduces their chance of organ preservation. Contact X-ray brachytherapy (CXB) or High Dose Rate Endo Brachy Therapy (HDREBT) boost following external beam radiotherapy can improve the initial cCR rate and reduce the risk of local regrowth. Those patients with persistent residual cancer or regrowth after brachytherapy boost following EBCRT or EBRT can have salvage surgery later without compromising their chance of cure. Therefore, patients should be fully aware of their treatment options and have 'a choice' when deciding and consenting their treatment.

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.

International audience; We examined whether 66 germline single-nucleotide polymorphisms (SNPs) in 10 candidate genes would predict clinical outcome in 316 patients with resectable locally advanced rectal cancer (LARC) enrolled in the ACCORD-12 phase III trial who were randomly treated with preoperative radiotherapy plus capecitabine (CAP45; n = 155) or dose-intensified radiotherapy plus capecitabine and oxaliplatin (CAPOX50; n = 161). The primary endpoint was tumor response according to the Dworak score. Multivariate logistic regression models adjusted on treatment arm and T stage determined the SNPs prognostic and predictive values for tumor response. In univariate analysis, five SNPs in ERCC2, XPA, MTHFR and ERCC1 were associated with the Dworak score in the CAPOX50 arm. In the overall population, interaction with treatment arm was significant for ERCC2 rs1799787 (pinteraction = 0.05) and XPA rs3176683 (pinteraction = 0.008), suggesting a predictive effect for response to oxaliplatin-based chemoradiotherapy (CRT). All but XPA rs3176683 had a prognostic effect on tumor response. In a multivariate model, interaction remained significant for XPA rs3176683 ([OR 7.33, 95% CI 1.40-38.23], pinteraction = 0.018) and the prognostic effect significant for ERCC2 rs1799787 ([OR 0.55, 95%CI 0.32-0.93], p = 0.027) and ERCC1 rs10412761 ([OR 0.57, 95%CI 0.34-0.98], p = 0.042). Patients with the T/G haplotype of rs1799787 and rs10412761 had a 60% decrease in odds of response (p

Neoadjuvant chemoradiotherapy (nCRT) and watch-and-wait policy as reported by Habr-Gama are references for organ preservation in rectal cancer. To increase the clinical complete response (cCR) and reduce the local recurrence rates, we report a retrospective analysis of a prospective cohort of selected T2-3 tumours treated in three French institutions using contact X-ray brachytherapy (CXB) with nCRT.Tumour selection was based on digital rectal examination (DRE), rigid rectoscopy, magnetic resonance imaging (MRI) and/or endorectal ultrasound. Adenocarcinoma T2-35 cm largest diameter, M0 were treated, all with organ preservation intent. CXB delivering 90 Gy/3 fractions/4 weeks was combined with CRT (capecitabine 50). Strict evaluation of tumour response using DRE and rectoscopy ± MRI was performed at regular interval with prolonged surveillance.Between 2002 and 2016, 74 consecutive patients were treated (median age: 74 years. T2: 45 and T3: 29). A cCR or near-cCR (mainly rectal wall ulceration) was noted at week 14 in 71 patients (95%). A local excision was performed in 13 patients. Of three partial responses (PRs), one salvage anterior resection was performed. With a median follow-up of 3 years, local recurrence (mainly in the rectal wall) was seen in seven patients. The 3-year local recurrence rate was 10%, and the cancer-specific survival, 88%. Two patients underwent radical proctectomy for PR or local recurrence and 96% preserved their rectum. Grade III acute toxicity was recorded in five patients. Rectal bleeding was the main late toxicity (grade III in 12%). Bowel function was scored as good or excellent in 85% of patients.Combining CXB and nCRT in selected early T2-T3 rectal cancers may safely provide a high rate of cCR, organ preservation, and good bowel function with a risk of local recurrence below 15%. Such an approach could be offered to operable patients as a planned option for organ preservation.

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. Patients with early-stage rectal cancer might potentially benefit from treatment with an organ-sparing approach, which preserves quality of life owing to avoidance of the need for permanent colostomy. Trials conducted to investigate this have so far been hampered by considerable inter-trial heterogeneity in several key features. In this Consensus Statement, the authors provide guidance on the optimal end points, response assessment time points, follow-up procedures and quality of life measures in an attempt to improve the comparability of clinical research in this area. Yorkshire Cancer Research Academic Fellowship fund [L389AA]; Yorkshire Cancer Research; Cancer Research UKCancer Research UK [CRUK/28301]

The Papillon experience and the Lyon R96-02 trial have shown that contact X-ray brachytherapy of 50kV is efficient and safe to achieve long term local control and organ preservation for cT1 and early cT2-3 rectal cancers. The OPERA trial, using the Papillon 50™ machine, brings further support to this preservation strategy for selected T2T3ab lesions. Future trials using a contact X-ray boost will try to consolidate and enlarge its place in organ preservation for rectal cancers.

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 GRECCAR (Groupe de REcherche en Radiologie sur le CAncer du Rectum [i.e., Rectal Cancer Imaging Research Group]) and GRECAR (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 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.

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 MannWhitney 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. (C) 2020 Elsevier B.V. All rights reserved.

Cisplatin is one of the most commonly used chemotherapy in lung cancer despite its high nephrotoxicity leading to an administration only every 3–4 weeks. This study is the first report of a preclinical investigation of therapeutic intensification combining a cisplatin dry powder for inhalation (CIS-DPI) with an intravenous (iv) cisplatin-based treatment. CIS-DPI with 50% cisplatin content (CIS-DPI-50) was developed using lipid excipients through scalable processes (high-speed and high-pressure homogenization and spray-drying). CIS-DPI-50 showed good aerodynamic performance (fine particle fraction of ~ 55% and a mass median aerodynamic particle size of ~ 2 µm) and a seven-fold increase and decrease in Cmax in the lungs and in plasma, respectively, in comparison with an iv cisplatin solution (CIS-iv) in healthy mice. Finally, the addition of CIS-DPI-50 to the standard cisplatin/paclitaxel iv doublet increased the response rate (67% vs 50%), decreased the tumour growth and prolonged the median survival (31 vs 21 days), compared to the iv doublet in the M109 lung carcinoma model tending to demonstrate a therapeutic intensification of cisplatin., SCOPUS: ar.j, info:eu-repo/semantics/published

With an expanding elderly population and median rectal cancer detection age of 70 years, the prevalence of rectal cancer in elderly patients is increasing. Management is based on evidence from younger patients, resulting in substandard treatments and poor outcomes. Modern management of rectal cancer in the elderly demands patient-centered treatment, assessing frailty rather than chronological age. The heterogeneity of this group, combined with the limited available data, impedes drafting evidence based guidelines. Therefore, a multidisciplinary task force convened experts from the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology and the American College Surgeons Commission on Cancer, with the goal of identifying the best practice to promote personalized rectal cancer care in older patients. A crucial element for personalized care was recognized as the routine screening for frailty and geriatrician involvement and personalized care for frail patients. Careful patient selection and improved surgical and perioperative techniques are responsible for a substantial improvement in rectal cancer outcomes. Therefore, properly selected patients should be considered for surgical resection. Local excision can be utilized when balancing oncologic outcomes, frailty and life expectancy. Watch and wait protocols, in expert hands, are valuable for selected patients and adjuncts can be added to improve complete response rates. Functional recovery and patient-reported outcomes are as important as oncologic-specific outcomes in this age group. The above recommendations and others were made based on the best-available evidence to guide the personalized treatment of elderly patients with rectal cancer. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

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 (n1 = 131, n2 = 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.

Purpose The Lyon R90-01 randomized trial investigated whether the interval between preoperative radiation therapy and surgery influenced rectal cancer outcome. Long-term results are reported here after a median follow-up of 17 years. Methods and Materials Between February 1991 and December 1995, 210 patients from 29 French centers were randomly assigned (ratio of 1:1) to groups that waited either 2 weeks (short interval [SI]) or 6 to 8 weeks (long interval [LI]) between neoadjuvant radiation therapy and surgery. The primary endpoint was sphincter-preserving surgery. Results LI group showed a better pathologic response (complete response or few residual cells) after radiation therapy than the SI group (26% vs 10.3%, P =.015). A better pathologic response was associated in multivariate analysis with significant improvement of overall survival (pT: P =.0293 and pN: P =.0048) but it was irrespective of the interval duration. The median follow-up was 17.2 years. The 5-, 10-, 15-, and 17-year overall survival rates were, respectively, 66.8%, 48.7%, 40.0%, and 34.0% for the SI group and, respectively, 67.1%, 53.5%, 41.9%, and 34.0% for the LI group. There were no significant differences between groups in terms of survival ( P =.7656) or local recurrence rates (SI: 14.4% vs LI: 12.1%, respectively; P =.6202). Of 24 local disease recurrences, 20 (83%) occurred during the first 2 postoperative years, and all but one (96%) occurred during the first 5 postoperative years. The rate of second new malignancies was 9.4% (19 patients). Conclusions The radiation-induced sterilization rate of the preoperative cancer specimen was a marker of good prognosis. The interval duration (the treatment being the same) although it is modifying the sterilization rate has no impact on survival. Radiation therapy did not postpone local recurrence, because the rate of local relapse after 5 years was low. Radiation-induced cancers after radiation therapy were unusual and should not influence treatment decisions in adults.

12 Background: Non-operative modality (NOM) treatment of rectal cancer is gaining popularity as it avoids extirpative TME surgery and a stoma. OPERA trial was set up to evaluate the role of dose escalation using Contact X-ray brachytherapy [CXB] in improving the chance of organ preservation compared to the standard of care (EBCRT and TME surgery). We report on the preliminary surgical salvage data for treatment failures in the OPERA trial (NCT02505750). Methods: OPERA is a European phase 3 randomised trial between (Arm A- standard arm) EBCRT 45Gy/25/5weeks with oral capecitabine 825mg/m2 and EBRT boost of 9Gy/5/5 days randomised against (Arm B- experimental arm) EBCRT followed by CXB boost (90 Gy/3/4 weeks). Patients were assessed at 14, 20 and 24 weeks. Watch & wait policy was adopted for patients with cCR at 24 weeks after randomisation and surgery (TME or local excision) was offered for residual disease and also for local regrowth (recurrence) at a later date. Results: From July 2015 –June 2020, 148 patients were randomised of which 144 were evaluable (table). There were 71 patients in Arm A (standard) and 73 patients in Arm B (experimental). Median follow-up was 19 months (range 2-36 m). Overall clinical complete response (cCR) was observed in 103 out of 127 evaluable patients (81%) at 24 week in both arms (blinded). Surgery was carried out in 36/ 127 (28%) patients with suspected residual tumour. Further 13 patients had salvage surgery at a later date for local regrowth. At 19 months, 49/144 (34%) patients in total cohort had surgery. Local excision was carried out in 24 /49(49%) of which 3 proceeded to TME surgery due to R (1) or ypT2 adverse histology. TME surgery was carried out in 28/49 of which 8/28 (28.6%) had APER and 20/28(71.4%) had AR. In total, organ preservation (blinded) was achieved in 116/144 (80.5%) for the whole cohort. Kaplan Meier estimate of TME free survival is 76% at 19 months. Conclusions: Non-TME surgical treatment for cT2-cT3a-b rectal cancer is feasible in those who are fit and wish to avoid surgery (Watch & Wait). Those who needed surgery can be offered salvage surgery immediately for local residual disease or for local regrowth at a later date. Organ preservation of 80.5% (blinded) can be achieved without compromising their chance of cure. Clinical trial information: NCT02505750. [Table: see text]

Purpose The aim of this study was to evaluate the efficacy and toxicity of high-dose-rate brachytherapy (HDR-BT) boost in anal squamous cell carcinoma (ASCC). Material and methods This was a monocentric retrospective study involving patients treated by external irradiation (± chemotherapy), with HDR-BT boost, for a localized ASCC. Clinical evaluation was performed every six months. Oncological results were analyzed with: local relapse-free survival (LRFS), colostomy-free survival (CFS), metastatic-free survival (MFS), disease-free survival (DFS), and overall survival (OS). Acute and late toxicities were collected (CTCV4.0) and LENT/SOMA score was performed. Results From May 2005 to January 2018, 46 patients (pts) were analyzed. The median follow-up was 61 months (10-145 months), the median age was 65 years (34-84 years), with a sex ratio M/F = 0.24. The TNM classification was as follows: T1 - 13 pts (21.7%), T2 - 34 pts (73.9%), T3 - 2 pts (4.3%), N+ - 6 pts (13.1%). External beam radiotherapy (EBRT) delivered a median dose of 45 Gy (36-50.4 Gy) in 25 fractions, and HDR-BT 12 Gy (10-18 Gy) in 3 fractions. The median overall treatment time (OTT) was 58 days (41-101 days), with a median EBRT/brachytherapy interval of 17 days (4-60 days). Oncological findings showed 5-year rates of LRFS 81.2%, MFS 88.7%, DFS 70%, and OS 90%. All abdominoperineal amputations were performed in case of local relapse (4 pts, 8.7%), leading to a 5-year CFS of 79.5%. Acute urinary toxicities were frequent (G1 41.3%, G2 4.3%). The acute digestive toxicities were: G1 71.7%, G2 6.5%, and G3 2.2%. The late urinary toxicities were: G1 4.3%, G2 2.2%, and G3 2.2%. Late digestive toxicities were: G1 56.5%, G2 8.7%, G3 2.2%, and G4 2.2%. Conclusions In ASCC management, HDR-BT boost appears to be a treatment with a long-term acceptable toxicity profile, shorter than EBRT boost, with a reduction of side effects.

Resume Objectif de l’etude Cette etude retrospective a evalue les modalites de prise en charge et le pronostic des cancers du rectum chez le sujet âge en comparaison avec ceux des sujets plus jeunes. Patients et methodes Les donnees de 160 patients de plus 80 ans, ayant recu un traitement pour un cancer du rectum diagnostique entre 2006 et 2008, en region Provence-Alpes-Cote-d’Azur, independamment du stade et du traitement de la maladie ont ete analysees retrospectivement. Les taux de survie globale et sans rechute ont ete correles avec les caracteristiques de la tumeur et les traitements administres. Le traitement administre a ensuite ete compare aux standards therapeutiques recommandes pour les patients plus jeunes. Resultats Avec 36 mois de suivi median, les taux de survie globale et sans rechute a 3 ans etaient respectivement de 59,2 % et 76,6 % pour les 117 patients ayant recu un traitement a visee curative. En analyse multifactorielle, la survie globale etait independamment influencee par le statut N et l’exerese chirurgicale, alors que la survie sans rechute etait influencee par l’âge, le statut N, et le sexe. Les tumeurs de stade T0–T2 ont ete traitees conformement aux recommandations pour les patients plus jeunes, avec respectivement des taux a 3 ans de 83,6 % et 95,2 % de survie globale et de survie sans rechute. Pour les patients atteints de tumeur de stade T3–T4, le taux de survie sans rechute a 3 ans etait de 65 %, malgre une strategie moins agressive. Conclusion Sous reserve d’une bonne evaluation oncogeriatrique, la chirurgie reste le standard de traitement des tumeurs localisees (de stade T0–T2) des patients âges. Pour les tumeurs localement evoluees (de stade T3–T4), les resultats obtenus dans cette etude suggerent qu’une approche conservatrice pourrait etre envisagee.

Rectal cancers stages II–III are presenting many various clinical situations. Neoadjuvant chemoradiotherapy is a standard of care in many cases, and in association with TME surgery, local relapses are becoming uncommon. None of these neoadjuvant treatments have so far improved survival, and quality of life remains non-optimal after abdomino-perineal resection and quite often after anterior resection. To increase survival through sterilization of subclinical distant metastases, new induction chemotherapy is tested. In T4 tumors, radiation dose escalation should be able to further improve local control, and in elderly patients, reduction of nCRT toxicity may provide better compliance to TME surgery. A promising approach is the use of optimal neoadjuvant treatment in early tumors in order to achieve a clinical complete response and propose an organ preservation either after local excision or using a meticulous and prolonged watch and wait strategy. Well-conducted randomized trials will be necessary to modify the present standard of care.

Background During the ACCORD 12 randomized trial, an evaluation of the clinical tumor response was prospectively performed after neoadjuvant chemoradiotherapy. The correlations between clinical complete response and patient characteristics and treatment outcomes are reported. Material and methods Between 2005 and 2008 the Accord 12 trial accrued 598 patients with locally advanced rectal cancer and compared two different neoadjuvant chemoradiotherapies (Capox 50: capecitabine+oxaliplatin+50Gy vs Cap 45: capecitabine+45Gy). An evaluation of the clinical tumor response with rectoscopy and digital rectal examination was planned before surgery. A score to classify tumor response was used adapted from the RECIST definition: complete response: no visible or palpable tumor; partial response, stable and progressive disease. Results The clinical tumor response was evaluable in 201 patients. Score was: complete response: 8% (16 patients); partial response: 68% (137 patients); stable: 21%; progression: 3%. There was a trend toward more complete response in the Capox 50 group (9.3% vs 6.7% with Cap 45). In the whole cohort of 201 pts complete response was significantly more frequent in T2 tumors (28%; p =0.025); tumors p =0.017), less than half rectal circumference and with a normal CEA level. Clinical complete response observed in 16 patients was associated with more conservative treatment ( p =0.008): 2 patients required an abdomino-perineal resection, 11 an anterior resection and 3 patients benefited from organ preservation (2 local excision, 1 "watch and wait". A complete response was associated with more ypT0 (73%; p Conclusion These data support the hypothesis that a clinical complete response assessed using rectoscopy and digital rectal examination after neoadjuvant therapy may increase the chance of a sphincter or organ preservation in selected rectal cancers.

Purpose Personalized treatments based on predictions for patient outcome require early characterization of a rectal cancer patient’s sensitivity to treatment. This study has two aims: (1) identify the main patterns of recurrence and response to the treatments (2) evaluate pathologic complete response (pCR) and two-year disease-free survival (2yDFS) for overall survival (OS) and their potential to be relevant intermediate endpoints to predict. Methods Pooled and treatment subgroup analyses were performed on five large European rectal cancer trials (2795 patients), who all received long-course radiotherapy with or without concomitant and/or adjuvant chemotherapy. The ratio of distant metastasis (DM) and local recurrence (LR) rates was used to identify patient characteristics that increase the risk of recurrences. Findings The DM/LR ratio decreased to a plateau in the first 2 years, revealing it to be a critical follow-up period. According to the patterns of recurrences, three patient groups were identified: 5–15% had pCR and were disease free after 2 years (excellent prognosis), 65–75% had no pCR but were disease free (good prognosis) and 15–30% had neither pCR nor 2yDFS (poor prognosis). Interpretation Compared with pCR, 2yDFS is a stronger predictor of OS. To adapt treatment most efficiently, accurate prediction models should be developed for pCR to select patients for organ preservation and for 2yDFS to select patients for more intensified treatment strategies.

Information concerning management of anal canal cancer among the elderly is scarce and much less abundant than for younger subjects.We retrospectively analysed 115 patients treated for anal epidermoid cancer between 2000 and 2010. The population was divided according to age (70 years and ≥70 years).Of the 115 patients, 81 (70.4%) were70 years old and 34 were ≥70 years (29.6%). Tumour characteristics were identical between the two groups and median follow-up was 62 months. Elderly patients had a less favourable performance status (p=0.001) and fewer had received radiochemotherapy (61.8% vs 82.5%, p=0.004). Treatment-related grade 3 and 4 hematologic toxicity was observed more often among elderly subjects. The results at 5 years were less favourable for overall, disease-specific, and disease-free survival (respectively p=0.002, p=0.001, and p=0.001). For patients treated with a curative intent, at 5 years there was no difference between the two groups in terms of overall survival (p=0.2). However, there was a statistically significant difference in favour of the younger group for disease-free survival and metastasis-free survival.If radiochemotherapy can be delivered to elderly subjects with a good general status, the effects appear less favourable than in younger patients.

This study aimed to determine the candidate genes and chromosomal imbalances capable of predicting occurrences of metastasis in patients with rectal cancer. Fresh frozen tumor tissues from 80 patients with rectal cancer were prospectively collected and analyzed using Affymetrix HG-U133 Plus 2.0 gene expression arrays and high-resolution Illumina single-nucleotide polymorphism (SNP) arrays. Endpoints of the study were metastasis-free survival (MFS) and cancer-specific survival (CSS). The median follow-up was 102 months (1–146). Deletions of 8p and 1p36-35 correlated with worse MFS (p = 0.005 and p = 0.01, respectively) and CSS (p = 0.001 and p = 0.01, respectively). Multivariate analysis identified 8p deletion as an independent prognostic factor for MFS (p = 0.04) and CSS (p = 0.003); 97 genes located on the 8p chromosome were significantly underexpressed in tumors with 8p deletion. This study shows for the first time in rectal cancer an independent correlation of 8p deletion with MFS and CSS and highlights potential new tumor suppressor genes.

2628 Background: We investigated whether an adaptation to rectal biopsies of the recently validated consensus Immunoscore, could predict the response to neoadjuvant treatment and delineate clinical responders that could benefit from a “Watch and Wait” (W&W) strategy with acceptable outcomes. Methods: Initial biopsies from 273 patients with locally advanced rectal cancer (LARC) treated by neoadjuvant chemoradiotherapy (nCRT) followed by Total Mesorectal Excision (TME), were immunostained for CD3+ and cytotoxic CD8+ T cells and quantified by digital pathology to determine the Immunoscore within pre-treatment Biopsy (ISB). Expression level of 44 immune related genes post-neoadjuvant treatment was investigated by Nanostring technology (n = 64 patients). Results were correlated with response to neoadjuvant treatment, disease free survival (DFS) and time to recurrence (TTR). Prognostic performance of ISB was finally assessed in 73 LARC treated by W&W strategy. Results: ISB Low, Intermediate and High were respectively observed in 23.3, 50.4 and 26.3 % of the cohort. ISB was positively and significantly correlated with the response to nCRT, as evaluated by Dworak classification (P = .0034), ypTNM (P = .0003), down-staging (P = .0014), and neoadjuvant rectal (NAR) score, (P < .0001). ISB status was also positively associated with the degree of local immune activation post-neoadjuvant treatment. ISB High patients were at low risk of relapse, with 5-year DFS rates of 81.1 % (CI, 71.3-92.1 %) as compared to 57.8 % (CI, 45.9-72.9 %) in ISB low patients. In multivariate analysis, ISB was the only significant parameter at presentation associated with DFS (High vs Low: P = .001). Among W&W patients, significant difference was observed for TTR according to ISB status (High vs Low: P = .025). Conclusions: ISB could provide a reliable estimate of the response to nCRT and risk of recurrence in LARC patients' treated by TME or W&W strategy.

BACKGROUND The treatment of anal cancer is based on concomitant radiotherapy and chemotherapy and is associated with a nonnegligible rate of local severe toxicities that can strongly impair the quality of life. OBJECTIVE A retrospective analysis was performed to screen the following factors as potential predictive factors for local skin and digestive toxicities, and as potential prognostic factors for cumulative colostomy incidence: sex, age, tumor size, clinical T and N stage, circumferential extension, invasion of anal margin, HIV status, type of chemotherapy, and type of radiotherapy and dose delivered. METHODS One hundred five patients in our database treated between January 2000 and February 2010 met the eligibility criteria. RESULTS Median follow-up was 54.1 months (range, 1-133). Early and late severe local toxicities occurred in 33 patients (31.4%) and 18 patients (17.1%). The 5-year cumulative rate of colostomy was 26.6%. Predictive factors for local severe early toxicities were as follows: clinical stage III/IV (p = 0.01), no brachytherapy boost (p = 0.003), and use of chemotherapy (p = 0.01). Only brachytherapy retained its independence in multivariate analysis (OR = 4.8 (1.4-16.3), p = 0.01). Human immunodeficiency virus positivity (p = 0.04) was the only predictive factor for late toxicities in univariate analysis; it was linked independently to the occurrence of ulcer (OR = 0.1 (0.01-0.66), p = 0.01). Tumor size ≥4 cm (p < 0.001) and occurrence of grade 2 to 3 ulcers (p < 0.001) were correlated with greater cumulative colostomy incidence. CONCLUSIONS In this cohort, nonuse of brachytherapy was an independent predictive factor for local acute toxicity. Human immunodeficiency virus positivity was the only predictive factor for local late toxicities and strongly influenced the onset of ulcer.

Low dose-rate brachytherapy as a boost after concomitant chemoradiation therapy is a standard of care for locally advanced anal carcinoma, providing a rigorous selection taking into account the initial staging and tumor response to external beam radiotherapy. Local control is likely to be superior when the boost is performed with brachytherapy than with external beam radiotherapy. The several steps of the brachytherapy procedure are described. The standard treatment scheme is a concomitant chemoradiation therapy, including 45 Gy (1,8 Gy × 5) pelvic external beam radiotherapy and two courses of 5-fluorouracil and mitomycin-C, followed by a 15 Gy brachytherapy boost with a gap limited to 2 to 3 weeks. Higher irradiation dose for the most advanced cases has not yet demonstrated a therapeutic gain in terms of colostomy free survival. Exclusive brachytherapy for in-situ carcinoma or invasive carcinoma less than 10mm is not recommended due to a high risk of local recurrence. Pulsed dose rate brachytherapy is an alternative to low dose rate brachytherapy (iridium wires) providing the respect of the recommended dose rate (0.5 to 1 Gy/hour). High dose rate brachytherapy is still under evaluation.

IF 3.061; International audience; IntroductionThis document is a summary of the French Intergroup guidelines regarding the management of rectal adenocarcinoma published in February 2016.MethodThis collaborative work, under the auspices of most of the French medical societies involved in the management of rectal cancer, is based on the previous guidelines published in 2013. Recommendations are graded into 3 categories according to the level of evidence of data found in the literature.ResultsIn agreement with the ESMO guidelines (2013), non-metastatic rectal cancers have been stratified in 4 risk groups according to endoscopy, MRI or endorectal-ultrasonography. Locally-advanced tumors are limited to groups 3 and 4 (T3 ≥4 cm or T3c–d or N1-2 or T4). These tumors are usually treated using neoadjuvant treatment and total proctectomy (TME). Adjuvant treatment depends on the pathological findings. Very early (group 1) or early (group 2) tumors are managed mainly by surgery, and organ preservation may be an option in selected cases. For metastatic tumors, the recommendations are based on less robust evidence and chemotherapy plays a major role.ConclusionSuch recommendations are constantly being optimized and each individual case must be discussed within a Multi-Disciplinary Team.

Background Contact X-ray brachytherapy (CXB) has been used at Centre Antoine Lacassagne since 2002 to increase the chance of conservative treatment (organ or sphincter preservation) in rectal cancer. A consecutive series of 112 patients (pts) is reported. Methods Three protocols were used in selected rectal adenocarcinomas. Group 1: T1 N0 treated with local excision (LE) followed by adjuvant CXB. Group 2: T2 or ‘early’ T3 N0 treated with CXB combined with chemoradiotherapy (CRT) followed by surveillance or LE. Group 3: distal ‘locally advanced’ T3 N0-2 treated with CXB and CRT before total proctectomy. Results Group 1: 27 pt (pTis: 3; pT1: 21; pT2: 3). After LE with CXB alone (20 pt) or CXB + CRT (7 pt) one local recurrence occurred. Organ preservation was achieved in 26 pt (96%). Group 2: 45 pt (T1: 2; T2: 23; T3: 20) treated with CXB alone (4 pt) or CXB + CRT or external beam radiotherapy (EBRT) (41 pt). A clinical complete response (cCR) was observed in 43/45 (96%) and 3 pt developed a local recurrence (11% at 5 years). The specific survival was 76% at 5 years and the rate of organ preservation was 89% (40/45 pt) with good bowel function in 36 pt. Group 3: 40 pt, anterior resection (with sphincter preservation) was possible in 35 pt (86%) with a 3-year local recurrence of 6%. Conclusion CXB usually combined as a boost with CRT or EBRT may safely increase the chance of a conservative treatment (organ or sphincter preservation) for selected rectal cancers.

Introduction Patients with metastatic colorectal cancer (CRC) may present with oligometastatic lung lesions for which stereotactic ablative radiotherapy (SABR) can be utilized. This study aims to report efficacy and prognostic factors associated with colorectal lung metastases treated with SABR. Material and Methods This is a retrospective study including patients who presented with lung oligometastasis from CRC treated with SABR from September 2007 to November 2014. Results We identified 53 oligometastatic patients with 87 lung lesions. The median prescription dose was 60 Gy in 3 fractions (median biological effective dose of 180 Gy). The median follow up was 33 months. The 1- and 2-year local control, metastasis-free survival, and overall survival were 79.8% and 78.2%, 29.2% and 16.2%, and 83.8% and 69.3%, respectively. On multivariate analysis, rectal primary site ( P = .001) and > 2 metastases ( P = .02) were significantly associated with a lower local control rate. Rectal lesions were associated with higher radiation dose (169.3 Gy vs. 153.3 Gy; P = .01) and higher rate of KRAS mutations (73.3% vs. 40.4%; P = .02). KRAS mutation did not predict for local control, but predicted for a 1-year metastasis-free survival detriment (0% vs. 37.5%; P = .04), when compared with KRAS wild-type. On multivariate analysis, there is an overall survival detriment associated with gross tumor volume ≥ 3266 mm 3 ( P = .03) and > 2 metastases ( P = .04). Conclusion In CRC, oligometastatic lung lesions treated with SABR had a worse outcome in patients presenting with a rectal primary, > 2 metastases, or treated with a larger gross tumor volume. More aggressive treatment may be considered in this subset of patients to improve outcome.

Contains fulltext : 171468pub.pdf (Publisher’s version ) (Open Access) Primary treatment of rectal cancer was the focus of the second St. Gallen European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Conference. In the context of the conference, a multidisciplinary international expert panel discussed and voted on controversial issues which could not be easily answered using published evidence. Main topics included optimal pretherapeutic imaging, indication and type of neoadjuvant treatment, and the treatment strategies in advanced tumours. Here we report the key recommendations and summarise the related evidence. The treatment strategy for localised rectal cancer varies from local excision in early tumours to neoadjuvant radiochemotherapy (RCT) in combination with extended surgery in locally advanced disease. Optimal pretherapeutic staging is a key to any treatment decision. The panel recommended magnetic resonance imaging (MRI) or MRI + endoscopic ultrasonography (EUS) as mandatory staging modalities, except for early T1 cancers with an option for local excision, where EUS in addition to MRI was considered to be most important because of its superior near-field resolution. Primary surgery with total mesorectal excision was recommended by most panellists for some early tumours with limited risk of recurrence (i.e. cT1-2 or cT3a N0 with clear mesorectal fascia on MRI and clearly above the levator muscles), whereas all other stages were considered for multimodal treatment. The consensus panel recommended long-course RCT over short-course radiotherapy for most clinical situations where neoadjuvant treatment is indicated, with the exception of T3a/b N0 tumours where short-course radiotherapy or even no neoadjuvant therapy were regarded to be an option. In patients with potentially resectable tumours and synchronous liver metastases, most panel members did not see an indication to start with classical fluoropyrimidine-based RCT but rather favoured preoperative short-course radiotherapy with systemic combination chemotherapy or alternatively a liver-first resection approach in resectable metastases, which both allow optimal systemic therapy for the metastatic disease. In general, proper patient selection and discussion in an experienced multidisciplinary team was considered as crucial component of care.

Purpose In 1998 a translational research was initiated in Lyon aiming at identifying a prognostic “biomolecular signature” in rectal cancer. This paper presents the clinical outcome of the patients included in this study. Patients and methods A total of 94 patients were included between 1998 and 2001. A staging with rectoscopy and biopsies was performed before treatment. In case of surgery, the operative specimen was analysed to evaluate the pathological response. There were two types of treatment: neoadjuvant radiotherapy (with or without concurrent chemotherapy) followed by surgery (76 cases) and radiotherapy alone with ‘contactherapy’ often associated with external beam radiotherapy (18 patients). Results The patients had a mean age of 63 years. Stage was T1: 4, T2: 24, T3: 65 and T4: 1. The overall survival of the 94 patients was 62% at 8 years with a rate of distant metastases of 29%. Rate of local recurrence at 8 years was 6% in the neoadjuvant group and 16% in the radiotherapy group with an overall 8 years survival in both groups respectively: 64% and 53%. There was a trend towards more metastases in cT3, tumour diameter above 4 cm, circumferential extension. There was a significant increase in the risk of metastases for ypT3, ypN1-2 and Dworak score 1-2-3. In multivariate analysis ypT3 was significantly associated with a high rate of metastases (55%; P = 0.0003). Conclusion The rate of distant metastases is a major prognostic factor. These clinical results will serve as the base line to identify a “biomolecular signature” which could complement the TN(M) classification.

In the last 10 years, a number of important European randomized published studies investigated the optimal management of rectal cancer. In order to define an evidence-based approach of the clinical practice based, an international consensus conference was organized in Italy under the endorsement of European Society of Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO) and European Society of Therapeutic Radiation Oncology (ESTRO). The aim of this article is to present highlights of multidisciplinary rectal cancer management and to compare the conclusions of the international conference on 'Multidisciplinary Rectal Cancer Treatment: looking for an European Consensus' (EURECA-CC2) with the new National Comprehensive Cancer Network (NCCN) guidelines.

Radiotherapy has been driven by constant technological advances since the discovery of X-rays in 1895. Radiotherapy aims to sculpt the optimal isodose on the tumour volume while sparing normal tissues. The benefits are threefold: patient cure, organ preservation and cost-efficiency. The efficacy and tolerance of radiotherapy were demonstrated by randomized trials in many different types of cancer (including breast, prostate and rectum) with a high level of scientific evidence. Such achievements, of major importance for the quality of life of patients, have been fostered during the past decade by linear accelerators with computer-assisted technology. More recently, these developments were augmented by proton and particle beam radiotherapy, usually combined with surgery and medical treatment in a multidisciplinary and personalized strategy against cancer. This article reviews the timeline of 100 years of radiotherapy with a focus on breakthroughs in the physics of radiotherapy and technology during the past two decades, and the associated clinical benefits.

A differential responsiveness of patients to ionizing radiation is observed after preoperative radiotherapy for rectal adenocarcinoma that might be related, in part, to an apoptosis defect. To establish if proteins of the apoptotic cascades [pro-apoptotic: active caspase 3, 8, and 9 and DIABLO (direct inhibitor of apoptosis-binding protein with low pI); anti-apoptotic: XIAP (X-linked inhibitor of apoptosis)] are involved, we analyzed their profile in radioresistant (SW480) and radiosensitive (SW48) human colorectal cell lines. We demonstrated that, after irradiation, the SW48 cells increased the expression of the pro-apoptotic proteins, whereas the SW480 cells increased the expression of the anti-apoptotic protein XIAP. Moreover, XIAP knockdown in SW480 cells enhanced the basal and radiation-induced apoptotic index; the propensity of the SW480 cells to undergo apoptosis after radiation was higher compared with SW48 cells. In a translational study of 38 patients with rectal carcinoma, we analyzed the apoptotic profile for tumor and noncancerous tissue for each biopsy specimen using IHC. According to their response to preoperative radiotherapy, patients were classified into two groups: responsive and nonresponsive. Although no difference in expression of caspase 3, 8, or 9 was observed in the tumor/normal tissue ratio between responsive and nonresponsive patients, the ratio decreased for DIABLO and increased for XIAP. In conclusion, inhibition of XIAP rescues cellular radiosensitivity and both DIABLO and XIAP might be potential predictive markers of radiation responsiveness in rectal adenocarcinoma.

Purpose Concomitant radiochemotherapy (RCT) is the standard for locally advanced anal canal carcinoma (LAACC). Questions regarding the role of induction chemotherapy (ICT) and a higher radiation dose in LAACC are pending. Our trial was designed to determine whether dose escalation of the radiation boost or two cycles of ICT before concomitant RCT lead to an improvement in colostomy-free survival (CFS). Patients and Methods Patients with tumors ≥ 40 mm, or < 40 mm and N1-3M0 were randomly assigned to one of four treatment arms: (A) two ICT cycles (fluorouracil 800 mg/m2/d intravenous [IV] infusion, days 1 through 4 and 29 to 32; and cisplatin 80 mg/m2 IV, on days 1 and 29), RCT (45 Gy in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), and standard-dose boost (SD; 15 Gy); (B) two ICT cycles, RCT, and high-dose boost (HD; 20-25 Gy); (C): RCT and SD boost (reference arm); and (D) RCT and HD boost. Results Two hundred eighty-three of 307 patients achieved full treatment. With a median follow-up period of 50 months, the 5-year CFS rates were 69.6%, 82.4%, 77.1%, and 72.7% in arms A, B, C, and D, respectively. Considering the 2 × 2 factorial analysis, the 5-year CFS was 76.5% versus 75.0% (P = .37) in groups A and B versus C and D, respectively (ICT effect), and 73.7% versus 77.8% in groups A and C versus B and D, respectively (RT-dose effect; P = .067). Conclusion Using CFS as our main end point, we did not find an advantage for either ICT or HD radiation boost in LAACC. Nevertheless, the results of the most treatment-intense arm B should prompt the design of further intensification studies.

To investigate, in rectal cancer, the benefit of a neoadjuvant radiation dose escalation with endocavitary contact radiotherapy (CXRT) in addition to external beam radiotherapy (EBRT). This article provides an update of the Lyon R96-02 Phase III trial.A total of 88 patients with T2 to T3 carcinoma of the lower rectum were randomly assigned to neoadjuvant EBRT 39 Gy in 13 fractions (43 patients) vs. the same EBRT with CXRT boost, 85 Gy in three fractions (45 patients). Median follow-up was 132 months.The 10-year cumulated rate of permanent colostomy (CRPC) was 63% in the EBRT group vs. 29% in the EBRT+CXRT group (p0.001). The 10-year rate of local recurrence was 15% vs. 10% (p = 0.69); 10-year disease-free survival was 54% vs. 53% (p = 0.99); and 10-year overall survival was 56% vs. 55% (p = 0.85). Data of clinical response (CR) were available for 78 patients (36 in the EBRT group and 42 in the EBRT+CXRT group): 12 patients were in complete CR (1 patient vs. 11 patients), 53 patients had a CR ≥ 50% (24 patients vs. 29 patients), and 13 patients had a CR50% (11 patients vs. 2 patients) (p0.001). Of the 65 patients with CR ≥ 50%, 9 had an organ preservation procedure (meaning no rectal resection) taking advantage of major CR. The 10-year CRPC was 17% for patients with complete CR, 42% for patients with CR ≥ 50%, and 77% for patients with CR50% (p = 0.014).In cancer of the lower rectum, CXRT increases the complete CR, turning in a significantly higher rate of long-term permanent sphincter and organ preservation.

Purpose A common hypothesis is that neo-adjuvant treatment in rectal cancer, is able to increase sphincter saving surgery. This review studies data relevant to this question. Study selection A total of 17 randomized trials were analysed. Results Since 1976, the rate of sphincter saving surgery increased from 20% to 75%. In none of the 17 trials it was possible to demonstrate a significant benefit of the neo-adjuvant regimens on the rate of sphincter saving surgery. There was a reduction in the risk of 5-year local recurrence partly due to these neo-adjuvant treatments. These neo-adjuvant regimens had no significant impact on the overall 5-year survival. Conclusions None of the neo-adjuvant treatments tested was able to demonstrate an increase in the rate of sphincter saving surgery. The improvement in conservative surgery is mainly due to technical changes in surgery. Organ preservation after complete clinical response appears as an interesting hypothesis to test.

Purpose A clinical complete response is seen after neoadjuvant chemoradiation for rectal tumors in 15%–20% of patients. These patients can potentially be spared mutilating total mesorectal excision surgery through a watch-and-wait policy. Recent studies show that dose escalation by a radiation boost increases the clinical complete response rate. The boost dose to the tumor can be administered through external beam radiotherapy or through internal radiotherapy using techniques like contact therapy, low-dose-rate or high-dose-rate brachytherapy (BT). However, limited information is available concerning treatment-related toxicity of these techniques. With this systematic review, we aim to summarize and compare published data concerning acute and late toxicity after contact X-ray therapy (CXT) and BT for rectal cancer. Methods and Materials/Results Thirty-eight studies reporting toxicity after endorectal radiation techniques for rectal cancer were included, resulting in 3682 patients for analysis. Direct comparison of toxicity by the different radiation modes was hampered by various combinations of endorectal techniques, a lack of clear reporting of toxicity scores, dose prescription, technique used, and treated volumes. ≥ Grade 3 rectal toxicity was reported in 2.9% of patients having received only CXT; 6.3% of patients who received only BT had Grade 3 rectal toxicity, and BT also caused Grade 3 urinary toxicity in 1 patient. Conclusion All techniques reported some ≥ Grade 3 toxicity. Toxicity after CXT was confined to the rectum, whereas after BT, urogenital toxicity and skin toxicity were seen as well. Unfortunately, few specific conclusions could be drawn regarding the dose-related risk of toxicity for the various techniques due to nonuniform reporting strategies and missing information. To enable future comparisons and improvements, the endorectal radiation field urgently needs consensus guidelines on dose reporting, dose prescription, treatment volume specification, and toxicity reporting.