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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.

Pelvic fixation in patients with neuromuscular scoliosis is difficult, due to their fragile general condition and poor bone quality. Many techniques have been described, associated with high rates of mechanical complications. The objective of this work was to evaluate the mechanical complications and long-term radiological results of ilio-sacral screw pelvic fixation.167 consecutive patients with neuromuscular scoliosis who underwent minimally invasive bipolar fixation with ilio-sacral screw pelvic fixation were retrospectively reviewed. The instrumentation consisted in a bilateral sliding rods construct extended from T1 to the sacrum, anchored proximally by double-hook claws and distally by ilio-sacral screws through a minimally invasive approach. Mechanical complications and radiographic measurements (angle of the major coronal curve, pelvic obliquity, lumbar lordosis) were evaluated preoperatively, postoperatively, and at the last follow-up.Mean operative age was 12 ± 3 years, and follow-up 6.4 years (3.0-10.4 years). Pelvic obliquity decreased from 20° preoperatively to 5° (77% correction) at last follow-up, Angle of the major coronal curve from 75° to 36° (52% correction), and lumbar lordosis from 28° to 38°. 16 mechanical complications in nine patients occurred: screw prominence (n = 1), connector failure (n = 4), screw malposition (n = 11). Unplanned surgery was required in seven cases, two were managed during rod lengthening, seven did not require treatment.In this series of neuromuscular patients operated by ilio-sacral screws as pelvic fixation, the results were stable with a mean follow-up of more than 6 years and the complication rate was reduced comparatively to the literature.4.

BACKGROUND: The strategy of watch and wait (W&W) in patients with rectal cancer who achieve a complete clinical response (cCR) after neoadjuvant therapy is new and offers an opportunity for patients to avoid major resection surgery. However, evidence is based on small-to-moderate sized series from specialist centres. The International Watch & Wait Database (IWWD) aims to describe the outcome of the W&W strategy in a large-scale registry of pooled individual patient data. We report the results of a descriptive analysis after inclusion of more than 1000 patients in the registry.METHODS: Participating centres entered data in the registry through an online, highly secured, and encrypted research data server. Data included baseline characteristics, neoadjuvant therapy, imaging protocols, incidence of local regrowth and distant metastasis, and survival status. All patients with rectal cancer in whom the standard of care (total mesorectal excision surgery) was omitted after neoadjuvant therapy were eligible to be included in the IWWD. For the present analysis, we only selected patients with no signs of residual tumour at reassessment (a cCR). We analysed the proportion of patients with local regrowth, proportion of patients with distant metastases, 5-year overall survival, and 5-year disease-specific survival.FINDINGS: Between April 14, 2015, and June 30, 2017, we identified 1009 patients who received neoadjuvant treatment and were managed by W&W in the database from 47 participating institutes (15 countries). We included 880 (87%) patients with a cCR. Median follow-up time was 3·3 years (95% CI 3·1-3·6). The 2-year cumulative incidence of local regrowth was 25·2% (95% CI 22·2-28·5%), 88% of all local regrowth was diagnosed in the first 2 years, and 97% of local regrowth was located in the bowel wall. Distant metastasis were diagnosed in 71 (8%) of 880 patients. 5-year overall survival was 85% (95% CI 80·9-87·7%), and 5-year disease-specific survival was 94% (91-96%).INTERPRETATION: This dataset has the largest series of patients with rectal cancer treated with a W&W approach, consisting of approximately 50% data from previous cohort series and 50% unpublished data. Local regrowth occurs mostly in the first 2 years and in the bowel wall, emphasising the importance of endoscopic surveillance to ensure the option of deferred curative surgery. Local unsalvageable disease after W&W was rare.FUNDING: European Registration of Cancer Care financed by European Society of Surgical Oncology, Champalimaud Foundation Lisbon, Bas Mulder Award granted by the Alpe d'Huzes Foundation and Dutch Cancer Society, and European Research Council Advanced Grant.

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 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]

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.

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.

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.

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.

Neoadjuvant chemoradiotherapy is considered at the present time as the standard treatment of most T3-4 rectal cancer. In France a combination of radiotherapy (45 Gy/5 weeks) with concurrent capecitabine (1,600 mg/m2) is the most popular protocol. Randomized trials try to optimize this approach using new cytotoxic drugs and/or radiation dose-escalation. The introduction of biotargeted therapies (anti-EGFR or antiangiogenic) is an attractive field especially selecting the treatment according to K-ras mutation. For T2 and 'early T3' present studies are using neoadjuvant chemoradiation followed by transanal local excision in case of good tumor response. In frail elderly patients, a new trend is to use mainly exclusive irradiation to control the tumor and avoid the excessive toxicity of open surgery in this group of patients. As rectal cancer is presenting many different clinical situations, an individualised treatment appears justified.

The mathematical relationship between the dose to the parotid glands and salivary gland production needs to be elucidated. This study, which included data from patients included in a French prospective study assessing the benefit of intensity-modulated radiotherapy (RT), sought to elaborate a convenient and original model of salivary recovery.Between January 2001 and December 2004, 44 patients were included (35 with oropharyngeal and 9 with nasopharyngeal cancer). Of the 44 patients, 24 were treated with intensity-modulated RT, 17 with three-dimensional conformal RT, and 2 with two-dimensional RT. Stimulated salivary production was collected for/=24 months after RT. The data of salivary production, time of follow-up, and dose to parotid gland were modeled using a mixed model. Several models were developed to assess the best-fitting variable for the dose level to the parotid gland.Models developed with the dose to the contralateral parotid fit the data slightly better than those with the dose to both parotids, suggesting that contralateral and ipsilateral parotid glands are not functionally equivalent even with the same dose level to the glands. The best predictive dose-value variable for salivary flow recovery was the volume of the contralateral parotid gland receiving40 Gy.The results of this study show that the recommendation of a dose constraint for intensity-modulated RT planning should be established at the volume of the contralateral parotid gland receiving40 Gy rather than the mean dose. For complete salivary production recovery after 24 months, the volume of the contralateral parotid gland receiving40 Gy should be33%. Our results permitted us to establish two convenient tools to predict the saliva production recovery function according to the dose received by the contralateral parotid gland.

Although contact radiotherapy was developed 70 years ago, and is highly effective with cure rates of over 90% for early rectal cancer, there are few centres that offer this treatment today. One reason is the lack of replacement of ageing contact X-ray machines, many of which are now over 30 years old. To address this problem, the International Contact Radiotherapy Evaluation (ICONE) group was formed at a meeting in Liverpool in 2005 with the aim of developing a new contact X-ray unit and to establish clinical protocols that would enable the new machine to safely engage in the treatment of rectal cancer. As a result of these efforts, a European company is starting production of the new Papillon RT-50 machine, which will be available shortly. In addition, the ICONE group is planning an observational study on contact X-ray and transanal endoscopic microsurgery (CONTEM) for curative treatment of rectal cancer. This protocol will ensure standardised diagnostic procedures, patient selection and treatment in centres across the world and the data will be collected prospectively for analysis and audit. It is hoped that the CONTEM trial will provide the scientific evidence that is needed to obtain a broader acceptance of local contact radiotherapy as a treatment option for selected cases with early stage rectal cancer. Udgivelsesdato: 2007-Nov

Attempts to increase survival in stage III ovarian cancer patients with minimal residual disease at second-look laparotomy have included consolidation radiotherapy. We present long-term survival of 106 consecutive patients treated between 1983 and 1993 in 4 French institutions for stage III ovarian adenocarcinoma with first-look debulking, cisplatin-based chemotherapy, second-look surgery with a residual disease1 cm and consolidation radiotherapy.Median age was 52 years. Residual disease after first look surgery was1 cm for 40.5% of patients. Median number of chemotherapy cycles was 6 (range 4-12). Residual disease1 cm at second-look laparotomy was observed in 79% of the patients, with 33% of patients in complete histologic remission. Residual disease1 cm was obtained in all patients after tumor excision during second-look surgery. Radiation was performed using a linear accelerator with a whole abdomen dose of 22.5 Gy, an additional 22 Gy pelvic boost for 71 patients, and an additional 12 Gy lombo-aortic boost for 33 patients.Median follow-up was 14 years. Radiation was stopped for acute toxicity in 11 patients. Long-term toxicities included radiation enteritis in 21 patients with 9 patients requiring surgery for bowel obstruction. Four deaths were related to enteritis complications. Overall survival at 5 and 10 years was respectively 53% and 36%.This sequential treatment with final consolidation abdominopelvic radiotherapy is an effective treatment for a selected group of stage III ovarian cancer patients with a high intestinal toxicity incidence.

In rectal cancer, the problem of sphincter preservation is of increasing interest. This paper is a review of recent data regarding sphincter preservation. Randomized trials give the best evidence of any improvement in sphincter preservation. Such trials have been performed for T3 and T2 rectal cancers. For T2-3 rectal tumors immediate surgery after preoperative radiotherapy or the addition of chemotherapy to radiotherapy did not improve the chance of sphincter preservation. Only dose escalation with endocavitary contact x-ray and delayed surgery was able to achieve a 30% increase in sphincter preservation. Ongoing clinical research is exploring the role of preoperative chemoradiotherapy in early T2 (T3) rectal cancers combined with local excision. This approach is of special interest in elderly patients. Sphincter preservation is a very complex issue in rectal cancer requiring great clinical experience to select properly the patients to perform the optimal treatment.

To report our patient experience with squamous cell carcinoma of the anal margin and to evaluate the prognostic factors influencing outcome. Between 1980 and 2001, 26 patients with anal margin squamous cell carcinoma were treated in Lyon-Sud: 7 T1, 14 T2, 4 T3, and 1 T4 with 20 N0, 3 N1, and 3 N2. The anal canal was invaded in five patients. Treatment consisted of definitive external irradiation in 14 patients and adjuvant irradiation (after a local excision) in 12 patients. External irradiation was combined with chemotherapy in seven patients, brachytherapy in four patients, and both brachytherapy and chemotherapy in one patient. The local control rate was initially 61.4%, and it was 80.8% after salvage treatment. The 5-year overall and specific survival rates were 71 and 88.3%, respectively. Three factors correlated with specific survival: cell differentiation (P=0.038) and T (P=0.001) and N category (P=0.0005). A salvage abdominoperineal resection was successfully employed in five of seven local recurrences. Four grade 3 and two grade 4 toxicities were observed. Sphincter preservation was possible in 66% of alive patients. Our results confirm the dominating place of definitive irradiation and radiochemotherapy in the treatment of anal margin squamous cell carcinoma. The indications for abdominoperineal resection must be limited to local relapse. The prognosis of squamous cell carcinoma is correlated to T and N staging and cell differentiation.

Purpose: To evaluate whether the tumor response after an initial course of irradiation predicts for colostomy-free survival and overall survival in patients with anal canal cancer. Methods and Materials: Between 1980 and 1998, 252 patients were treated by pelvic external-beam radiotherapy (EBRT) followed by a brachytherapy boost in 218 or EBRT in 34. EBRT was combined with chemotherapy in 168 patients. An evaluation of tumor regression, before the boost, was available for 221 patients. They were divided into four groups according to the tumor response: 80% but Results: The median follow-up time was 58 months. The overall survival rate was 72.6% ± 3.1% and 57.3% ± 4.2% at 5 and 10 years, respectively. The disease-free survival rate was 60.0% ± 3.3% and 49.4% ± 3.9% at 5 and 10 years, respectively. The colostomy-free survival rate was 61% at 5 years and 47% at 10 years. Two groups could be differentiated according to the percentage of tumor regression before the boost: >80% vs. ≤80%. The group with a T3-T4 lesion and tumor regression ≤80% had the poorest overall (52.8% ± 12.3%), disease-free (19.9% ± 9.9%), and colostomy-free survival (24.8% ± 11.2%) rates. Conclusion: The amount of tumor regression before EBRT or brachytherapy boost is a strong prognostic factor of disease control without colostomy. When regression is ≤80% in patients with an initial T3-T4 lesion, the use of conservative RT should be carefully evaluated because of the very poor disease-free and colostomy-free survival.

Background and purpose During the past decades staging and treatment of rectal cancer are used different in Europe and in North America. To promote a process to integrate the daily practice with the best evidence of the literature an International Conference was organized in Italy. Agreement between Experts, Centres, and specialists who participated in the Conference are reported. Methods Five aspects were analyzed and a questionnaire was tailored for this purpose. The questionnaire had 159 questions. During the Conference, at the beginning of each Session, the moderators showed the answers from the Experts and the Centres, and, at the end of the session, the audience voted in all controversial issues. Agreements were scored at three levels: minimum, if it was between 51 and 74% of votes for each group; moderate, between 75 and 94%; large, more than 94%. Results The main results are: staging : endoanal ultrasound was considered as mandatory in T staging, in the evaluation of sphincter infiltration, and in the restaging of T after chemoradiotherapy (chRT). Magnetic Resonance Imaging is mandatory in the evaluation of mesorectal fascia infiltration. Endoscopy had a moderate agreement for the definition of tumour location, and the barium enema as optional. Digital rectal examination is complementary for staging and PET-CT investigational for T, N and yT staging. Preoperative radiotherapy : for T4 stage chRT was always the preferred treatment, often with moderate agreement, for any tumour location and N status. For T3, chRT received the same agreement except for high location and N0-N1. For T2 stage, N2 and positive nodes outside the mesorectum, chRT received minimum agreement for low and middle tumours; for high tumours only positive nodes outside the mesorectum was agreed upon. Preoperative radiotherapy, negative specimen and sphincter preservation : chRT was agreed by many for all T stages and N presentations of lower third tumours, except for T1-2 N0-N1. Postoperative treatments : the selection for these treatments often received moderate agreement according to the infiltration of surrounding organs, positive nodal status and circumferential radial margins. Therapy of metastatic disease : an agreement was found for FOLFOX as first-line therapy and for FOLFIRI as second-line, although comparaitive studies show similar activity of FOLFOX and FOLFIRI regimens. Conclusions This process represents an expertise opinion process that may contribute to increased scientific debate and to promote the development of ‘guidelines', ‘clinical recommendations' and ultimately a Consensus on the evolving approach to rectal cancer treatment.

This retrospective 12-year study evaluated the prognostic value of initial and postoperative staging of rectal tumors.Between 1985 and 1996, 297 patients were treated with preoperative radiotherapy (39 Gy in 13 fractions) and surgery for Stage T2-T4N0-N1M0 rectal adenocarcinoma. Pretreatment staging included a clinical examination and endorectal ultrasonography (EUS) since 1988. Clinical staging was performed by digital rectal examination and rigid proctoscopy. EUS was performed in 236 patients. Postoperative staging was performed by examination of the pathologic specimen.The median follow-up was 49 months. The overall 5-year survival rate was 67%, with a local failure rate of 9%. The rate of sphincter preservation was 65%. The clinical examination findings were strong prognostic factor for both cT stage (p0.001) and cN stage (p0.006) but had poor specificity for cN stage (only 25 lymph nodes detected). In both univariate and multivariate analyses, EUS had a statistically significant prognostic value for uT (p0.014) but not for uN (p0.47) stage. In contrast, pT and pN stages were strong prognostic factors (p0.001 and p0.001, respectively).Pretreatment staging, including clinical examination and EUS, seemed accurate enough to present a high prognostic value for the T stage. EUS was insufficient to stage lymph node involvement. Owing to its lack of specificity, uN stage was not a reliable prognostic factor. An improvement in N staging is necessary and essential. Despite downstaging, postoperative staging remained a very strong prognostic factor for both T and N stages.

Over the past 20 years there have been many advances in the management of rectal cancer. The medico-surgical school in Lyon, France, has a long tradition in managing this malignancy. The progression of ideas and practices requires a better knowledge of the patterns of tumor spread and local recurrence. Technical advances have greatly helped to facilitate sphincter preservation. Advances in radiotherapy have led to its routine use in the preoperative period. This approach has now emerged as the best therapeutic sequence. Our experience concerns 46 patients with low rectal carcinoma treated with this strategy. There were no post-operative deaths and no leakage. One patient (2%) had a pelvic abscess. Median follow-up was 50 months (1-151). At five years, the local recurrence rate was 8.5% and the actuarial survival rate was 72%, with a local control rate of 91%. Functional outcome, evaluated with a scoring system, was good in 60% of cases at one year and 78% at 5 years. Quality of life, evaluated with the American Society of Colon and Rectal Surgeons scale (A.S.C.R.S.), was 107 +/- 21 (range 33-140). The absence of defunctioning stoma (initial or late), good sexual and urinary well-being, and psychologic assessment are essential factors, requiring rigorous evaluation before the operation and specialized management after the operation. The proposed strategy based on this safe procedure and "French-type" neoadjuvant radiotherapy, permits sphincter preservation in patients with T2 and T3 tumors located near the dentate line, with good late oncological outcome. It is often amenable to the laparoscopic approach.

Aims: To report outcomes of adults with retroperitoneal sarcoma (RS) treated by surgery, external beam radiotherapy (EBRT) and intraoperative electron beam radiotherapy (IORT). Methods: From July 1988 to February 2001; 24 patients with primary and recurrent RS were diagnosed and treated. The median dose and energy of IORT delivered was 15Gy/9meV. EBRT dose varies between 45–50Gy. Results: There were five primary and 19 recurrent tumours. One primary and five recurrent tumours underwent R0 resection. There were 12 liposarcomas and 19 grade I tumours; 13 patients developed local recurrence and three developed distant metastases. Twenty-two patients received IORT associated with EBRT: 11 developed recurrences. Six patients developed Neurotoxicity (4 grade II and 2 grade III). Disease free survival and overall survival at 5 years was 28 and 56% respectively. Conclusions: EBRT with IORT treatment is a promising technique for local control. Lower recurrence rates are associated with radical (R0) surgical procedures.

To analyze the long-term result of patients presenting with T2-T3 rectal adenocarcinoma treated with curative intent by radiotherapy (RT) alone, using a combination of contact RT, external beam RT, and brachytherapy with an iridium implant. Patients were considered unsuitable for surgery because of the presence of severe comorbidity or because they did not consent to surgery and the possibility of a permanent stoma.Between 1986 and 1998, 63 patients (56 staged with endorectal ultrasonography) were entered into a pilot study. Patients had to have T2-T3, N0-N1, M0 adenocarcinoma of the middle or lower rectum involving less than two-thirds of the circumference. RT began with contact X-rays (80 Gy in 3 fractions for 21 days), followed by external beam RT (39 Gy in 13 fractions for 17 days) with a concomitant boost (4 Gy in 4 fractions). After a 4-6-week interval, an iridium implant delivered a completion dose of 20 Gy to the tumor. No chemotherapy was given.The median age of the patients was 72 years. Of the 63 patients, 41 had T2 and 22 had T3 tumors. The mean distance of the tumor from the anal verge was 3.6 cm. All patients completed treatment according to the protocol, except for 7 for whom brachytherapy was not performed. With a median follow-up time of 54 months, the primary local tumor control rate was 63%; after salvage surgery, the ultimate pelvic control was 73% (46 of 63). The 5-year overall survival rate was 64.4%, and for 42 patients aged80 years, it was 78% with 10 patients alive and well ator =10 years. No severe Grade 3-4 toxicity was seen. Acute proctitis was seen in most patients but did not require treatment interruption. Late rectal bleeding occurred in 24 patients. Only 1 required blood transfusion. Good anorectal function was maintained in 92% of living patients. The T stage was a strong prognostic factor, with a 5-year overall survival rate of 84% and 53% for T2 and T3 lesions, respectively, in patients80 years old.This is the first report of long-term local control and survival for ultrasound-staged T2-T3 rectal adenocarcinoma treated by RT alone, showing that high-dose irradiation to a small volume can provide a high therapeutic ratio for such tumors.

To the Editor, In most institutions, standard treatment of T2-T3 rectal adenocarcinoma is radical surgery using total mesorectal excision (TME) with or without neo-adjuvant treatment [radiotherapy ...

Over the past century, surgery has been the mainstay of rectal cancer management and will remain so for the foreseeable future. However, surgical mortality and morbidity is high, especially for the elderly patients. The population is ageing globally, the effect being more pronounced in Western countries. It is important to avoid extirpative surgery, especially in elderly patients, to deter surgical harm. National bowel cancer screening programmes around the world have helped to diagnose rectal cancer in its early stages. It is important to treat the early stages of the disease differently from the more advanced stages. Most protocols are bias heavily towards surgical management for rectal tumors. National and international consensus guidelines do not take into consideration the advancing age of the general population and recommend surgery as the gold standard of care. There is an urgent need to consider alternative treatment options that avoid extirpative surgery and stoma in the early stages of rectal cancer in the elderly.

BACKGROUND The authors performed a specific analysis of the clinical significance of inguinal lymph nodes metastases in patients with anal canal carcinoma (ACC). METHODS A retrospective analysis was conducted of 270 patients who were treated in Lyon between 1980 and 1996 with radiotherapy with curative intent for ACC: No elective irradiation of clinically normal inguinal areas was performed. Patients with metastatic inguinal lymph nodes were treated with inguinal dissection and postoperative irradiation with a dose of 50 grays over 5 weeks. Concomitant chemoradiation, usually with a regimen of fluorouracil and cisplatinum, was given to 159 patients. RESULTS The median follow-up for the whole series was 72 months. Synchronous inguinal metastases were observed in 10% of patients (n = 27; the rate was 16% for patients with T3–T4 lesions), and the 5-year overall survival rate was 54.4%. Metachronous inguinal metastases were seen in 19 patients (7.8%), and the 5-year overall survival rate of these patients was 41.4%. An original finding was that, when the primary tumor clearly was located on a single lateral side of the anal canal, the inguinal lymphatic metastases was always homolateral to it (36 of 36 synchronous plus metachronous tumors). CONCLUSIONS The data from this series of patients and a review of the literature are in favor of a selective approach in the management of inguinal lymph node involvement for patients with ACC, depending on the disease stage and the location of the primary tumors. Cancer 2001;92:77–84. © 2001 American Cancer Society.

Background: The aim of this study was to assess functional outcomes of patients who had a delayed coloanal anastomosis for a lower third rectal cancer after preoperative radiotherapy. Study Design: From January 1988 to December 1997, 35 patients with an adenocarcinoma of the lower third of the rectum received preoperative radiotherapy (45 Gy) followed by a rectal resection, combining an abdominal and transanal approach. Colorectal resection was performed about 32 days after the end of the radiotherapy. The distal colon stump was pulled through the anal canal. On postoperative day 5 the colonic stump was resected and a direct coloanal anastomosis performed without colostomia diversion. Results: There was no mortality. There was no leakage. One patient had a pelvic abscess. One patient had a necrosis of the left colon requiring reoperation. Another delayed coloanal anastomosis could be performed. Median followup was 43 months (range 6 to 113 months). Functional results were evaluated with a new scoring system including 13 items. Function was considered good in 59% and 70% at 1 and 2 years, respectively. Conclusions: This new procedure is a safe and effective sphincter-preserving operation that avoids a diverting stoma for patients with rectal cancer of the lower third of the rectum. This technique is well adapted for patients receiving preoperative radiotherapy, with low local morbidity and good functional results. Further adaptation could be imagined for a coelioscopic approach.

Background: Radical prostatectomy and external beam radiation therapy (EBRT) are the mainstays of treatment of prostate cancer with curative intent. The possible development of radiation proctitis and rectal bleeding are major concerns when using EBRT. Recently, conformal radiotherapy has been introduced in an attempt to improve the results of EBRT. This paper presents an overview of the Lyon experience using standard EBRT with doses of 68 Gy, and reports the preliminary results of a study of conformal radiotherapy with dose escalation. Methods: From 1981 to 1995, EBRT was used to treat 231 patients with localized adenocarcinomas of the prostate. The dose of EBRT was 68 Gy/34 fractions/7 weeks using a four-field box technique with 18-MeV photons. A feasibility study of conformal radiotherapy was commenced in 1996. To date, 145 patients have been treated with doses escalating from 68 to 80 Gy. Results: In the EBRT group of 231 patients, the 5-year overall survival was 80.3%. Anorectal function was scored as excellent in 90% of patients. Rectal bleeding was seen in 14.3% of patients and required local treatment in only seven. In the group treated with conformal radiotherapy, the preliminary results indicate good early tolerance. Conclusion: The curative treatment of patients with prostate cancer using EBRT gives good long-term survival with low rectal toxicity. Conformal radiotherapy appears to be an interesting approach to improve local control and perhaps survival.

Purpose : To evaluate the long-term results of the treatment of anal canal carcinoma (ACC) with a combined concomitant radiochemotherapy (CCRT) treatment using fluorouracil (5 FU) and cisplatinum (CDDP) with a high dose of radiation therapy. Patients and methods : Between 1982 and 1993 a series of 95 patients were treated. Staging showed a majority of advanced squamous ACC, i.e. 6 T1, 47 T2, 28 T3, 14 T4, 53 N0, 32 N1, 6 N2 and 4 N3. Irradiation was done with high dose external beam radiation therapy (EBRT) followed by a boost with 192 Iridium implant. During EBRT all patients received one course of 5 FU continuous infusion (1 g/m 2 /day, days 1–4) and CDDP (25 mg/m 2 /day, bolus days 1–4). Results : The median follow-up time was 64 months. At 5 and 8 years the overall survival was 84 and 77%, the cancer specific survival was 90 and 86% and the colostomy-free survival was 71 and 67%, respectively. The stage and the response of the tumor after EBRT were of prognostic significance. Patients with pararectal lymph nodes had an overall 5-year survival of 76% (versus 88% for non-N1). Among 78 patients who preserved their anus, the anal sphincter function was excellent or good in 72 (92%). Conclusion : According to these results and recent randomized trials, CCRT appears as the standard treatment of ACC. Radical surgery should be reserved for local recurrence or persisting disease after irradiation. High dose irradiation in a small volume with concomitant 5 FU-CDDP appears to give a high rate of long-term local control and survival. Careful evaluation of pararectal nodes is essential for a good staging of the disease.

Endocavitary radiation therapy (Endo RT) is performed mainly with a contact x-ray tube. Interstitial brachy-therapy is a supplementary method to boost the tumor bed. Only strictly selected patients can be treated for cure by Endo RT. More than 1,000 patients have been treated in Europe and North America, since 1950. In T1 N0 adenocarcinoma, the primary local control rate is close to 90%. The overall 5-year survival is between 60% and 90% depending on patient selection. Careful follow-up is necessary because the majority of local failures can be salvaged, usually by radical surgery. The main advantages of Endo RT are a fully ambulatory and simple treatment that can be applied even in frail or elderly inoperable patients, a low risk of complications, and an inexpensive treatment. Results show it is possible to perform curative treatment in patients with more advanced rectal carcinoma. With the combination of external-beam radiation therapy and Endo RT in stage T2–3 N0-1 tumors, the primary local control rate is around 70%, and the incidence of severe radiation toxicity is less than 5%. Overall 5-year survival is between 50% and 70%. Endo RT can also be used as an adjuvant treatment after local excision, in the treatment of villous adenomas, and for palliation of advanced inoperable tumors.

Purpose: To describe the results of a series of 63 Western patients presenting with gastric adenocarcinoma and treated with surgery and intraoperative radiation therapy (IORT) over a 8-year period and to discuss the role of IORT when combined with limited lymph node dissection. Methods and Materials: From 1986 to 1993, 63 patients with gastric adenocarcinoma have been operated in the department of radiation oncology of the Hospices Civils de Lyon. The stage was: I in 17, II in 11, IIIA in 9, IIIB in 20, and IV in 6. The lymph node dissection was considered to be limited in 56 patients and extended in 7. The IORT dose ranged from 12 to 23 Gy (median: 15). Thirty patients also underwent a postoperative external beam irradiation with a standard dose of 44-46 Gy. Results: The postoperative mortality rate was 4.8%. The 5-year overall survival in the entire series was 47% and was 82, 55, 78, 20, and 0% in Stages I, II, IIIA, IIIB, and IV, respectively. Loco-regional relapse occurred in 15 of 63 patients and metastases in 15 of 63. Conclusion: In Western patients treated by gastrectomy for adenocarcinoma of the stomach, IORT combined with limited lymph node dissection may provide overall survival similar to that observed after gastrectomy with extended lymph node dissection but with less postoperative mortality.

Background and purpose : To evaluate the impact of intraoperative radiotherapy (IORT) combined with postoperative external beam irradiation in patients with pancreatic cancer treated with curative surgical resection. Materials and methods : From January 1986 to April 1995 25 patients (11 male and 14 female, median age 61 years) underwent a curative resection with IORT for pancreatic adenocarcinoma. The tumour was located in the head of the pancreatic gland in 22 patients, in the body in two patients and in the tail in one patient. The pathological stage was pT1 in nine patients, pT2 in nine patients, pT3 in seven patients, pN0 in 14 patients and pN1 in 11 patients. All the patients were pM0. A pancreaticoduodenectomy was performed in 22 patients, a distal pancreatectomy was performed in two patients and a total pancreatectomy was performed in one patient. The resection was considered to be complete in 20 patients. One patient had microscopic residual disease and gross residual disease was present in four patients. IORT using electrons with a median energy of 12 MeV was performed in all the patients with doses ranging from 12 to 25 Gy. Postoperative EBRT was delivered to 20 patients (median dose 44 Gy). Concurrent chemotherapy with 5-fluorouracil was given to seven patients. Results : The overall survival was 56% at 1 year, 20% at 2 years and 10% at 5 years. Nine local failures were observed. Twelve patients developed metastases without local recurrence. Twenty patients died from tumour progression and two patients died from early postoperative complications. Three patients are still alive; two patients in complete response at 17 and 94 months and one patient with hepatic metastases at 13 months. Conclusion : IORT after complete resection combined with postoperative external beam irradiation is feasible and well tolerated in patients with pancreatic adenocarcinoma.

Standard treatment for limited stage adenocarcinoma of the breast includes lumpectomy (or a quadrantectomy), axillary node dissection, regional radiation therapy and, if the prognostic factors are unfavourable, chemotherapy and/or hormone therapy. This is supported by the results of American and European randomised trials. There have been many attempts at improving the modalities of conservative surgery and postoperative radiation therapy in order to maximize local control and minimize late sequellae. It is also likely that induction chemotherapy and external beam radiotherapy applied in selected cases increase the proportion of patients who can be offered conservative surgery.

Purpose: Prognosis of recurrent cancer remains poor, mainly because of the difficulties of achieving a satisfactory local control. Intraoperative radiation therapy (IORT) allows for the delivery of a complementary single dose to the tumor residues or to the tumor bed and could be useful in a multimodal treatment. In an attempt to evaluate this interest, a ertrospective analysis of patients treated with IORT in six French hospitals has bee performed. Methods and Materials: Data have been collected in 73 patients (41 men), with a mean age of 62 years, treated with IORT. Initial rectal tumors were large (mean diameter: 45 mm), partialy or totally fixed to the contiguous structures in 39%, and withnodal involvement in 50% of the cases. Initial surgery had been a sphincter-sparing surgery in 67%; external radiation therapy had been delivered in 52%, and a chemotherapy had been given in 10% of the patients. Recurrences were isolated (without metastases) in 86%, and were posterior or postero-lateral in 55% of the cases. Surgery allowed for a complete macroscopical resection in 57%, a partial resection with gross residual disease in 29%, and no resection in 14% of the recurrences. Intraoperative radiation therapy was delivered in a dose of 10 to 25 Gy (mean 18.5) through localizators of a mean diameter of 75 mm (60 to 110). External radiation therapy, either preoperative or postoeratively was given to 30 patients without prior radiation therapy. Ten patients received additiona chemotherapy with 5-fluorouracil. Results: Four postoperative deaths occurred. Postoperative morbidity occurred in 16 patients and some complications were probably related to the IORT procedure. Four long-term complications were observed. Overall actuarial survival occurred in 72.4% of the patients at year, in 44.6% at 2 years, and 30.6% at 3 years. Twenty-one local failures have been observed. Actuarial local control occurred in 71.3% of the patients at 1 year, 47.7% at 2 years, and 31.3% at 3 years. Conclusion:Intraoperative radiation therapy is a complementary treatment for recurrences of rectal cancer. It provides encouraging results, particularly in some selected situations, when patients have not previously been treated with external radiation therapy. Further studies of multimodal treatmetns are necessary.

International audience; Circumferential resection margin (CRM) appears as a new powerful prognostic factor of survival after surgery for rectal cancer. We aimed to evaluate predictive factors of positive CRM following preoperative radiochemotherapy in a French trial. Patients with rectal cancer were randomised in long course preoperative radiotherapy 45 Gy plus capecitabine versus 50 Gy plus capecitabine and oxaliplatin. Mesorectal excision was performed 6 weeks after treatment. Impact of clinical, pathological and surgical variables on positive CRM (≤1 mm) were analysed by multivariate analysis. Of 565 randomised patients, CRM was recorded in 390 cases and was positive in 8% (30/390). Patients with 50 Gy plus capecitabine and oxaliplatin had a 6% rate of positive CRM while those treated by 45 Gy plus capecitabine had a 10% rate (p=0.128). Three independent predictive factors of positive CRM were identified: abdominoperineal resection (APR) (odds ratio OR=3.24; p=0.004), vascular tumour invasion (OR=2.78; p=0.026) and poor histological response (modified Dworak 0-2) (OR=9.01; p=0.003). Significant predictive factors of positive CRM are related to type of surgery, especially APR, and poor histological prognostic factors. Intensification of neoadjuvant radiochemotherapy does not seem to have a major role in this study.

490 Background: The ACCORD 12 randomized trial was aiming at improving ypCR by increasing the radiation dose and adding oxaliplatin (OX) to a standard RT 45 Gy with concurrent capecitabine. On short term benefit of OX was not demonstrated (Gérard JP et al. J Clin Oncol. 2010;28:1638-44) at 3 years no significant difference in clinical outcome was achieved (Gérard JP et al. J Clin Oncol. 2012;30:4558-65. François E et al. Radiother Oncol. 2014;110:144-9). This is an update of results at 5 years. Methods: Between 11/2005 and 07/2008, 598 patients were randomized. Inclusion criteria: adenocarcinoma of rectum accessible to digital examination, T3 Nx M0 (or T2 distal anterior rectum). Randomization was between two neoadjuvant treatments chemo radiotherapy: Cap45 (45 Gy + capecitabine) and Capox50 (50 Gy + cape. and oxaliplatin). Main end point was sterilization of the operative specimen. Bowel function for patients treated with anterior resection was analyzed with a global score (1 very poor to 7 excellent). A total of 253 patients received adjuvant chemotherapy usually with FOLFOX: 133 in Cap45, 120 in Capox50. Results: In the ITT population, with a median follow-up of 60 months, updated carcinologic results were calculated using the Kaplan-Meier method. Out of 299 pts randomized in CAP45 and 299 pts in CAPOX50 results were respectively the following 1) 5y-cumulative incidence of Loc. Recurrence : 8.8% vs 7.8% (p = 0.78 HR = 0.92 [0.51-1.66]) 2) 5y-cumulative incidence of dist metastasis : 29.3% vs 27.1% (p = 0.48 HR = 0.89 [0.62-1.54]) 3) 5y-disease free survival rate : 60.4% vs 64.7% (p = 0.25 HR = 0.86 [0.66-1.11]) 4) 5y-overall survival rate : 76.4% vs 81.9% (p = 0.06 HR = 0.71 [0.50-1.01]) 5) bowel function median score : 5.2 [1-7] vs 4.9 [1-7]. Conclusions: At 5 years there was no significant difference in terms of local recurrence or distant metastases rates between both regimens. The new finding is a trend for improved overall survival in the Capox 50 groups may be related to subsequent salvage secondary treatments. At time of meeting the prognostic factors will be available in details and these results put in perspective with other phase III trial testing the role of oxaliplatin in Europe and the US. Clinical trial information: NCT00227747.

Systemic metastases from ovarian carcinoma are frequent, but they seldom affect the central nervous system. We present here the case of a patient treated for an ovarian cancer by surgery and chemotherapy. Three months after the end of chemotherapy, the patient developed cerebral metastases from ovarian carcinoma (CMOC) treated by iterative surgery and and whole brain irradiation. As the frequency of solitary cerebral metastasis of ovarian cancer is higher than with other cancers, it is likely that they behave slightly differently. Literature analysis reveals an increase in the incidence of CMOC since the middle of the nineties. CMOC can occur during or after adjuvant chemotherapy and the best management strategies to better define determinants of survival for patients are not well known. It appears that a better outcome of CMOC may be obtained by an aggressive treatment, if possible, including surgery, radiotherapy, and chemotherapy. Taking into account the increase in the incidence of the CMOC and their early occurrence, some authors have proposed a prophylactic brain radiotherapy in patients who receive adjuvant chemotherapy.

To evaluate the efficacy of irradiation of internal mammary nodes (IMN) on 10-year overall survival in breast cancer patients after mastectomy.This multicenter phase 3 study enrolled patients with positive axillary nodes (pN+) or central/medial tumors with or without pN+. Other inclusion criteria were age75 and a Karnofsky index ≥70. All patients received postoperative irradiation of the chest wall and supraclavicular nodes and were randomly assigned to receive IMN irradiation or not. Randomization was stratified by tumor location (medial/central or lateral), axillary lymph node status, and adjuvant therapy (chemotherapy vs no chemotherapy). The prescribed dose of irradiation to the target volumes was 50 Gy or equivalent. The first 5 intercostal spaces were included in the IMN target volume, and two-thirds of the dose (31.5 Gy) was given by electrons. The primary outcome was overall survival at 10 years. Disease-free survival and toxicity were secondary outcomes.T total of 1334 patients were analyzed after a median follow-up of 11.3 years among the survivors. No benefit of IMN irradiation on the overall survival could be demonstrated: the 10-year overall survival was 59.3% in the IMN-nonirradiated group versus 62.6% in the IMN-irradiated group (P=.8). According to stratification factors, we defined 6 subgroups (medial/central or lateral tumor, pN0 [only for medial/central] or pN+, and chemotherapy or not). In all these subgroups, IMN irradiation did not significantly improve overall survival.In patients treated with 2-dimensional techniques, we failed to demonstrate a survival benefit for IMN irradiation. This study cannot rule out a moderate benefit, especially with more modern, conformal techniques applied to a higher risk population.

International audience; BACKGROUND: Two phase III trials of neoadjuvant treatment in T3-4 rectal cancer established that adding chemotherapy (CRT) to radiotherapy (RT) improves pathological complete response (pCR) and local control (LC). We combined trials to assess the clinical benefit of CRT on overall (OS) and progression free survival (PFS) and to explore the surrogacy of pCR and LC. PATIENTS AND METHODS: Individual patient data from European Organisation for Research and Treatment of Cancer (EORTC) 22921 (1011 patients) and FFCD 9203 (756 patients) were pooled. Meta-analysis methodology was used to compare neoadjuvant CRT to RT for OS, PFS LC and distant progression (DP). Weighted linear regression was used to estimate trial-level association (surrogacy R(2)) between treatment effects on candidate surrogate (pCR, LC, DP) and OS. RESULTS: The median follow-up was 5.6years. Compared to RT (881pts), CRT (886pts) did not prolong OS, DP or PFS. The 5-y OS-rate was 66.3% with CRT versus 65.9% in RT (hazard ratios (HR)=1.04 {0.88-1.21}). CRT significantly improved LC (HR=0.54, 95%confidence interval (CI): 0.41-0.72). PFS was validated as surrogate for OS with R(2)=0.88. Neoadjuvant treatment effects on LC (R(2)=0.17) or DP (R(2)=0.31) did not predict effects on OS. CONCLUSION: Preoperative CRT does not prolong OS or PFS. pCR or LC do not qualify as surrogate for PFS or OS while PFS is surrogate. Phase III trials should use OS or PFS as primary endpoint.

Nineteen patients (14 women, 5 men) received external radiation therapy (ERT) between 1980 and 1988 for gall-bladder carcinoma. Eleven patients had complete resection (cholecystectomy in eight cases), six incomplete gross resection and two only percutaneous transhepatic biliary drainage (PTBD). The modalities of ERT were variable and doses ranged from 30 Gy/10 fractions to 50 Gy/25 fractions. Among 11 patients with complete resection (9/11 with T1 or T2 stages), overall survival was 55% at 48 months and 36% at 60 months, median survival was 48 months and at the time of this report 3/11 patients were alive with no evidence of disease, 54, 65, 76 months after surgery, and eight dead of cancer 8-114 months. Local control was achieved in 66 patients with T1 or T2 stages. All eight patients who had palliative surgery or PTBD died of cancer after 4-20 months with median survival of 6 months. Three complications were noted: one gastric ulcer in the course of ERT (surgical treatment), one duodenal ulcer which occurred 6 months after completion of ERT (medical treatment) and one regressive radiation hepatitis. From this experience it appears that ERT in gall-bladder carcinoma is well tolerated, can obtain local control and prolonged survival after complete resection and good palliation in non-resectable tumors.

In France, the late Jean Papillon was responsible for much of the pioneering work in the radiotherapy treatment of patients with rectal cancer. This review is written in tribute to his contribution to, and vast experience in, the conservative management of this common tumour. It describes his protocols with minor modifications currently used at the Centre Hospitalier Lyon-Sud, France. In Lyon, pre-operative adjuvant irradiation is the preferred treatment for patients with T2 and T3 rectal cancer. Initial results suggest that this combined approach significantly improves the likelihood of successful sphincter preservation for patients with carcinoma of the lower third of the rectum. To date, the technique has given good local control with minimal postoperative morbidity and low mortality.

Purpose The purpose of this study was to develop accurate models and nomograms to predict local recurrence, distant metastases, and survival for patients with locally advanced rectal cancer treated with long-course chemoradiotherapy (CRT) followed by surgery and to allow for a selection of patients who may benefit most from postoperative adjuvant chemotherapy and close follow-up. Patients and Methods All data (N = 2,795) from five major European clinical trials for rectal cancer were pooled and used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from one trial was used as an external validation set. The variables used in the analysis were sex, age, clinical tumor stage stage, tumor location, radiotherapy dose, concurrent and adjuvant chemotherapy, surgery procedure, and pTNM stage. Model performance was evaluated by the concordance index (c-index). Risk group stratification was proposed for the nomograms. Results The nomograms are able to predict events with a c-index for external validation of local recurrence (LR; 0.68), distant metastases (DM; 0.73), and overall survival (OS; 0.70). Pathologic staging is essential for accurate prediction of long-term outcome. Both preoperative CRT and adjuvant chemotherapy have an added value when predicting LR, DM, and OS rates. The stratification in risk groups allows significant distinction between Kaplan-Meier curves for outcome. Conclusion The easy-to-use nomograms can predict LR, DM, and OS over a 5-year period after surgery. They may be used as decision support tools in future trials by using the three defined risk groups to select patients for postoperative chemotherapy and close follow-up ( http://www.predictcancer.org ).

†Contact x-ray therapy (CXRT) with 50 kV has proven to be an efficient radiation therapy technique to achieve local control and rectal preservation for early rectal adenocarcinoma. Despite these results, CXRT has not been used due to the shortage of the no longer manufactured Philips RT 50™ unit. Recently, a new CXRT machine (Papillon 50™) became available on the market. This machine delivers a beam of 50 kV with a dose rate close to 15 Gy/min and has a percentage depth dose of 50% at 6–7 mm. The applicator size varies from 2–3 cm in diameter. Due to the original design of the main tube, treatment delivery is quick and more comfortable for the patients. An online viewing system incorporated in the tube allows a good visualization of the tumor with improved accuracy of radiation delivery. An international collaborative trial (Contact Endoscopic Microsurgery [CONTEM]) was set up to accrue approximately 300 cases of rectal adenocarcinoma staged T1, T2 or early T3 tumors in the UK, France, Denmark and Sweden. This trial should confirm the role of CXRT in curative treatment with organ preservation for early rectal cancers.