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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., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Cutaneous basal or squamous cell carcinomas are frequent lesions, their prognosis being associated to local control. Surgery remains the standard of treatment, if a complete resection can be realized without impairment of cosmesis or function. Brachytherapy can be used in the other cases, and is especially well adapted to periorificial lesions of the face. It is mostly realized with low dose rate iridium wires, but can be done with high dose rate if outpatient treatment is preferred. It allows high local control rates with very few late complications. The indication has to be discussed as first line treatment, according to the patient's age and general condition, the characteristics of the lesion, and the risk of late cosmetic or functional side-effects of the different therapeutic options., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Stereotactic radiation therapy (SRT) is becoming more and more important in the treatment of inoperable patients with early stages of pulmonary carcinomas (T1-T2 N0M0). In certain cases, evaluation of the response is still problematical and it can be difficult to differentiate response from progression. The aim of this paper is to set out these various changes and to produce a protocol for optimal monitoring. By comparing our clinical experience with data from the literature, the main visual aspects on a CT scan are set out and illustrated for each clinical situation: radiation pneumonitis, radiation fibrosis, therapeutic response and progression. The literature was reviewed by querying the main databases and selecting papers concerning pulmonary SRT and post-therapeutic radiological appearance. CT appearance induced by SRT differs significantly from images after classic conformal radiation therapy, both morphologically and chronologically. In particular, the modifications induced by stereotactic radiation therapy are only seen in a limited volume surrounding the volume treated. Knowledge of the radiological criteria necessary to differentiate between a therapeutic response and recurrence is of major importance in the present context of increase in use of this technique., (Copyright © 2012 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Objective: To describe post-CyberKnife® imaging characteristics of liver metastases as an aid in assessing response to treatment, and a novel set of combined criteria (CC) as an alternative to response according to change in size (RECIST)., Subjects and Methods: Imaging data and medical records of 28 patients with 40 liver metastases treated with stereotactic body radiotherapy (SBRT) were reviewed. Tumor size, CT attenuation coefficient, and contrast enhancement of lesions were evaluated up to 2 years post SBRT. Rates of local control, progression-free survival, time to progression, and overall survival according to RECIST and CC were estimated., Results: Complete response (CR) was 3.6% (95% CI: 0.1-18%) and 18% (95% CI: 6-37%) according to RECIST and combined criteria, respectively. Two progressive diseases and two partial responses according to RECIST were classified as CR by the combined criteria and one stable response according to RECIST was classified as progressive by CC (Stuart-Maxwell test, p = 0.012). The disease control rate was 60.7% (95% CI: 41-78%) by RECIST and 64% (95% CI: 44%-81%) by CC., Conclusion: Use of response criteria based on change in size alone in the interpretation of liver response to SBRT may be inadequate. We propose a simple algorithm with a combination of criteria to better assess tumor response. Further studies are needed to confirm their validity.

Background: Merkel cell carcinoma (MCC), a rare and aggressive neuroendocrine tumour, appears primarily on sun-exposed areas in light-skinned elderly subjects. UV exposure and profound immunosuppression (particularly in a setting of solid organ transplantation, haematological malignancies, HIV) constitute the principal risk factors. The aetiopathogenesis of this cancer is not known, although a polyomavirus involved in the oncogenic process was recently discovered. The carcinogenic effect of ionizing radiation, while not clearly established, has been suspected in rare cases involving the onset of MCC in irradiated zones. We report a new case of case of MCC in a patient previously undergoing radiotherapy., Case Report: A 59-year-old-man underwent radiotherapy for a Darier-Ferrand dermatofibrosarcoma on the left shoulder and developed MCC at the same site 38 years later., Discussion: The time between radiotherapy and diagnosis of MCC, its site within the radiation field (radio-dermatitis), the description of similar cases in the literature concerning the onset of MCC in irradiated areas, and the known carcinogenic effects of ionizing radiation all militate strongly in favour of the radiation-induced nature of MCC., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Purpose: The ACCORD 12 trial investigated the value of two different preoperative chemoradiotherapy (CT-RT) regimens in T3-4 Nx M0 resectable rectal cancer. Clinical results are reported after follow-up of 3 years., Patients and Methods: Between November 2005 and July 2008, a total of 598 patients were randomly assigned to preoperative CT-RT with CAP45 (45-Gy RT for 5 weeks with concurrent capecitabine) or CAPOX50 (50-Gy RT for 5 weeks with concurrent capecitabine and oxaliplatin). Total mesorectal excision was planned 6 weeks after CT-RT. The primary end point was sterilization of the operative specimen, which was achieved in 13.9% versus 19.2% of patients, respectively (P = .09). Clinical results were analyzed for all randomly assigned patients according to the intention-to-treat principle., Results: At 3 years, there was no significant difference between CAP45 and CAPOX50 (cumulative incidence of local recurrence, 6.1% v 4.4%; overall survival, 87.6% v 88.3%; disease-free survival, 67.9% v 72.7%). Grade 3 to 4 toxicity was reported in four patients in the CAP45 group and in two patients in the CAPOX50 group. Bowel continence, erectile dysfunction, and social life disturbance were not different between groups. In multivariate analysis, the sterilization rate (Dworak score) of the operative specimen was the main significant prognostic factor (hazard ratio, 0.32; 95% CI, 0.21 to 0.50)., Conclusion: At 3 years, no significant difference in clinical outcome was achieved with the intensified CAPOX regimen. When compared with other recent randomized trials, these results indicate that concurrent administration of oxaliplatin and RT is not recommended.

Purpose: Robotic Stereotactic Body Radiation Therapy with real-time tumor tracking has shown encouraging results for hepatic tumors with good efficacy and low toxicity. We studied the factors associated with local control of primary or secondary hepatic lesions post-SBRT., Methods and Materials: Since 2007, 153 stereotactic liver treatments were administered to 120 patients using the CyberKnife® System. Ninety-nine liver metastases (72 patients), 48 hepatocellular carcinomas (42 patients), and six cholangiocarcinomas were treated. On average, three to four sessions were delivered over 12 days. Twenty-seven to 45 Gy was prescribed to the 80% isodose line. Margins consisted of 5 to 10 mm for clinical target volume (CTV) and 3 mm for planning target volume (PTV)., Results: Median size was 33 mm (range, 5-112 mm). Median gross tumor volume (GTV) was 32.38 cm3 (range, 0.2-499.5 cm3). Median total dose was 45 Gy in three fractions. Median minimum dose was 27 Gy in three fractions. With a median follow-up of 15.0 months, local control rates at one and two years were 84% and 74.6%, respectively. The factors associated with better local control were lesion size < 50 mm (p = 0.019), GTV volume (p < 0.05), PTV volume (p < 0.01) and two treatment factors: a total dose of 45 Gy and a dose-per-fraction of 15 Gy (p = 0.019)., Conclusions: Dose, tumor diameter and volume are prognostic factors for local control when a stereotactic radiation therapy for hepatic lesions is considered. These results should be considered in order to obtain a maximum therapeutic efficacy.

Purpose: The purpose of this study is to evaluate the feasibility, efficacy and toxicity of SBRT for treatment of unresectable hepatic or lung metastases regardless of their primary tumor site for patients who received prior systemic chemotherapy., Methods and Materials: Between July 2007 and June 2010, 90 patients were treated with the CyberKnife® SBRT system for hepatic or pulmonary metastatic lesions. Medical records were retrospectively reviewed. The endpoints of this study were local control, overall survival (OS), disease-free survival (DFS), local relapse free-survival (LRFS), and treatment toxicity., Results: A total of 113 liver and 26 lung metastatic lesions in 52 men (58%) and 38 women (42%) were treated. Median follow-up was 17 months. Median age at treatment was 65 years (range, 23-84 years). Primary cancers were 63 GI, three lung, eight breast, four melanoma, three neuro-endocrine tumors, and three sarcomas. Median diameter of the lesions was 28 mm (range, 7-110 mm) for liver and 12.5 mm (range, 5-63.5 mm) for lung. Local control rates at 1 and 2 years were 84.5% and 66.1%, respectively. Two-year overall survival rate was 70% (95% CI: 55-81%). The 1 and 2-year disease-free survival rates were 27% (95% CI: 18-37%) and 10% (95% CI: 4-20%), respectively. Median duration of disease-free survival was 6.7 months (95% CI: 5.1-9.5 months). Observed toxicities included grade 1-3 acute toxicities. One grade 3 and no grade 4 toxicity were reported., Conclusion: High-dose SBRT for metastatic lesions is both feasible and effective with high local control rates. Overall survival is comparable with other available techniques. Treatment is well tolerated with low toxicity rates. It could represent an interesting treatment option for oligometastatic patients not amenable to surgery, even when patients had been pre-treated with chemotherapy., Summary: Stereotactic body radiotherapy (SBRT) has previously been successfully used in the treatment of metastatic lesions. It could be considered as a curative option for oligometastatic patients. This retrospective study involved 90 patients, designed to test potential effectiveness of SBRT in the treatment of oligometastases irrespective of primary. Results suggest SBRT could be an effective treatment extending patients' life span. This treatment appears to be more effective when used prior to multiple systemic treatment regimens.

Purpose: Stereotactic body radiation therapy (SBRT) for early-stage lung cancer can be achieved with several methods: respiratory gating, body frame, or real-time target and motion tracking. Two target tracking methods are currently available with the CyberKnife® System: the first one, fiducial tracking, requires the use of radio-opaque markers implanted near or inside the tumor, while the other, Xsight® Lung Tracking System, (XLTS) is fiducial-free. With XLTS, targeting is synchronized directly with target motion, which occurs due to respiration. While the former method (fiducial tracking) is well documented, the clinical relevance of the latter (tracking without fiducials) has never been well described to this date., Patients and Methods: A study was performed at our department for each patient treated for lung cancer with CyberKnife using XLTS. Selection criteria were: primary or recurring T1 or T2 stage non-small-cell lung cancer (NSCLC) with 15-60 mm tumor size. Initial staging included CT-Scan and FDG-PET., Results: Fifty-one patients not amenable to surgery were treated with XLTS. Median follow-up was 15 months (range, 5-30 months). Median tumor size was 24 mm (range, 15-60 mm). Median total dose was 60 Gy (36-60 Gy) in three fractions. Actuarial overall survival was 85.5% (95% CI = 74.5-96%) at 1 year and 79.4% (95% CI = 64-94.8%) at 2 years. Actuarial local control rate was 92% (95% CI = 84-99%) at one 1 year and 86% (95% CI = 75-97%) at 2 years., Conclusion: Local control and overall survival rates were similar to previous reports that used fiducials for tumor tracking. Toxicity was lower than most studies since tumor tracking did not require fiducial implantion. This fiducial-free method for respiratory motion tracking is a valid option for the most fragile patients.

Purpose: The CyberKnife(®) system is a recent radiation therapy technique that allows treatment of liver lesions with real-time tracking. Because of its high precision, the dose administered to the tumor can be increased. We report Oscar-Lambret Cancer Centre experience in the treatment of primary and secondary liver lesions., Patients and Methods: It is a retrospective study analyzing all the patients who have been treated for their liver lesions since July 2007. A hundred and twenty patients have been treated: 42 for hepatocellular carcinoma, 72 for liver metastases and six for cholangiocarcinoma. Gold seeds need to be implanted before the treatment and are used as markers to follow the movement of the lesion due to respiration. On average, the treatment is administered in three to four sessions over 12 days. A total dose of 40 to 45 Gy at the 80% isodose is delivered. Local control and overall survival analysis with Log-rank is performed for each type of lesion., Results: Treatment tolerance is good. The most common toxicities are of digestive type, pain and asthenia. Six gastro-duodenal ulcers and two radiation-induced liver disease (RILD) were observed. At a median follow-up of 15 months, the local control rate is respectively of 80.4% and 72.5% at 1 and 2 years. Overall survival is 84.6 and 58.3% at 1 and 2 years. The local control is significantly better for the hepatocellular carcinoma and overall survival is significantly better for liver metastases (P<0.05). The local control rate and overall survival at 1 year for cholangiocarcinoma is 100%., Conclusion: CyberKnife(®) is a promising technique, well tolerated, with tumoral local control rates comparable to other techniques. Its advantage is that it is very minimally invasive delivered as an outpatient procedure in a frail population of patient (disease, age)., (Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To evaluate the outcome, tolerance, and toxicity of stereotactic body radiotherapy, using image-guided robotic radiation delivery, for the treatment of patients with unresectable liver metastases., Methods and Material: Patients were treated with real-time respiratory tracking between July 2007 and April 2009. Their records were retrospectively reviewed. Metastases from colorectal carcinoma and other primaries were not necessarily confined to liver. Toxicity was evaluated using National Cancer Institute Common Criteria for Adverse Events version 3.0., Results: Forty-two patients with 62 metastases were treated with two dose levels of 40 Gy in four Dose per Fraction (23) and 45 Gy in three Dose per Fraction (13). Median follow-up was 14.3 months (range, 3-23 months). Actuarial local control for 1 and 2 years was 90% and 86%, respectively. At last follow-up, 41 (66%) complete responses and eight (13%) partial responses were observed. Five lesions were stable. Nine lesions (13%) were locally progressed. Overall survival was 94% at 1 year and 48% at 2 years. The most common toxicity was Grade 1 or 2 nausea. One patient experienced Grade 3 epidermitis. The dose level did not significantly contribute to the outcome, toxicity, or survival., Conclusion: Image-guided robotic stereotactic body radiation therapy is feasible, safe, and effective, with encouraging local control. It provides a strong alternative for patients who cannot undergo surgery., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The first-line treatment of a pelvic recurrence in a previously irradiated area is surgery. Unfortunately, few patients are deemed operable, often due to the location of the recurrence, usually too close to the iliac vessels, or the associated surgical morbidity. The objective of this study is to test the viability of robotic image-guided radiotherapy as an alternative treatment in inoperable cases., Methods: Sixteen patients previously treated with radiotherapy were reirradiated with CyberKnife® for lateral pelvic lesions. Recurrences of primary rectal cancer (4 patients), anal canal (6), uterine cervix cancer (4), endometrial cancer (1), and bladder carcinoma (1) were treated. The median dose of the previous treatment was 45 Gy (EqD2 range: 20 to 96 Gy). A total dose of 36 Gy in six fractions was delivered with the CyberKnife over three weeks. The responses were evaluated according to RECIST criteria., Results: Median follow-up was 10.6 months (1.9 to 20.5 months). The actuarial local control rate was 51.4% at one year. Median disease-free survival was 8.3 months after CyberKnife treatment. The actuarial one-year survival rate was 46%. Acute tolerance was limited to digestive grade 1 and 2 toxicities., Conclusions: Robotic stereotactic radiotherapy can offer a short and well-tolerated treatment for lateral pelvic recurrences in previously irradiated areas in patients otherwise not treatable. Efficacy and toxicity need to be evaluated over the long term, but initial results are encouraging.

Purpose: To analyze the outcome after adjuvant radiation therapy with standard fractionation regimen in metastatic lymph nodes (LN) from cutaneous melanoma., Patients and Methods: 86 successive patients (57 men) were treated for locally advanced melanoma in our institution. 60 patients (69%) underwent LN dissection followed by radiation therapy (RT), while 26 patients (31%) had no radiotherapy., Results: The median number of resected LN was 12 (1 to 36) with 2 metastases (1 to 28). Median survival after the first relapse was 31.8 months. Extracapsular extension was a significant prognostic factor for regional control (p = 0.019). Median total dose was 50 Gy (30 to 70 Gy). A standard fractionation regimen was used (2 Gy/fraction). Median number of fractions was 25 (10 to 44 fractions). Patients were treated with five fractions/week. Patients with extracapsular extension treated with surgery followed by RT (total dose ≥50 Gy) had a better regional control than patients treated by surgery followed by RT with a total dose <50 Gy (80% vs. 35% at 5-year follow-up; p = 0.004)., Conclusion: Adjuvant radiotherapy was able to increase regional control in targeted sub-population (LN with extracapsular extension).

Purpose: Stereotactic radiation therapy using the CyberKnife(®) has been introduced in France in 2006. Two treatment modalities are currently available: the first one (Synchrony(®)) is a real-time fiducial-based target tracking system, while the other (Xsight Lung Tracking [XLT] System(®)) is completely fiducial-free., Patients and Methods: Sixty-eight patients were treated for a pulmonary tumor between June 2007 and November 2009. Since august 2008, the XLT System(®) was used for 26 patients. We report the necessary conditions for the XLT System (position, laterality and size of the tumor), the toxicity and outcome of this treatment., Results: Twenty-two patients were analyzed. Median follow-up was 6 months (min=3; max=16). Local control rate was 100%. The main toxicity was grade grade 1 pulmonary alveolitis (27%). No grade 3 or 4 toxicities were reported., Conclusion: The high local control rate and low toxicity obtained with the CyberKnife(®) XLT System(®) suggest that such treatment is an alternative for inoperable patients., (Copyright © 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Esophageal cancers are highly malignant tumours with often a poor prognostic, except for minimal lesions treated with surgery. Radiation therapy, or combined radiation and chemotherapy is the most used therapeutic modality, alone or before oesophagectomy. The delineation of target volumes is now more accurate owing the possibility to use routinely the new imaging techniques (mainly PET). The aim of this work is to precise the radio-anatomical particularities, the pattern of spread of esophageal cancer and the principles of 3D conformal radiotherapy illustrated with a clinical case., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Introduction: In Western countries, the number of frail elderly people with metastatic melanoma (MM) keeps increasing. Conventional chemotherapy frequently induces imbalance in frail physiological cases. We propose to treat these patients with oral metronomic cyclophosphamide., Patients and Methods: This retrospective study analyses the data of patients with unresectable MM who received 50 to 100 mg of cyclophosphamide a day, 3 weeks out of 4. Main evaluation criterion was safety. Secondary evaluation criteria were objective response rate and overall survival., Results: Thirteen patients were included (median age: 80, 5 AJCC stage III and 8 AJCC stage IV). Clinical and biological safety were good, leading to long home staying and rare treatment discontinuations. Main toxicity observed was lymphopenia; no opportunist infection occurred. The control rate was 46%: one partial response and five stable diseases (median: 10 months). Survival after beginning of treatment ranged from 4 to 37 months (median: 8 months)., Discussion: Literature about MM in frail elderly is limited. Still, specific treatment is necessary. Cyclophosphamide in metronomic schema was well tolerated. The response rate was difficult to assess (small population) but several patients presented with long lasting stabilisation. The mechanisms of action of this treatment are original, associating antiangiogenic action and immunomodulation., Conclusion: Cyclophosphamide in metronomic schema showed good safety results for this frail population. Oral treatment enabled patients to stay at home longer and limited hospitalisation time. A larger controlled study will be necessary to confirm these encouraging results in elderly with MM, a classical chemoresistant tumor.

The liver is a large abdominal organ in the right hypondrium. Because of its anatomical situation, it is near many abdominal PTVs as well as some lower thoracic PVTs. The liver could also be at the same time the target (for irradiation of liver metastases or primary liver tumours) and organ at risk (OAR). Radiation-induced liver disease (RILD) is radiobiologically the normal tissue complication probability (NTCP), i.e., the clinical event limiting the total dose that could be delivered. This review describes radiobiological criteria justifying the NTCP data, and recommendations for conformal 3D radiotherapy and stereotactic liver irradiation., (Copyright (c) 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: Neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin., Patients and Methods: We randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m(2) twice daily 5 days per week (Cap 45) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m(2) twice daily 5 days per week and oxaliplatin 50 mg/m(2) once weekly (Capox 50). The primary end point was complete sterilization of the operative specimen (ypCR)., Results: Five hundred ninety-eight patients were randomly assigned to receive Cap 45 (n = 299) or Capox 50 (n = 299). More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group (25 v 1%; P < .001). Surgery was performed in 98% of patients in both groups. There were no differences between groups in the rate of conservative surgery (75%) or postoperative deaths at 60 days (0.3%). The ypCR rate was 13.9% with Cap 45 and 19.2% with Capox 50 (P = .09). When ypCR was combined with yp few residual cells, the rate was respectively 28.9% with Cap 45 and 39.4% with Capox 50 (P = .008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P = .02)., Conclusion: The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation. Cap 50 merits investigation for T3-4 rectal cancers.

Background: To the best of our knowledge, only 52 cases of squamous cell carcinoma (SCC) complicating hidradenitis suppurativa (HS) have been reported since 1958. We describe 13 new cases., Methods: We propose a clinical and histological analysis of our cases. We include these results in a review of previously reported cases to analyze a total of 65 patients. In our series of 13 cases, we also investigate the presence of human papillomavirus (HPV) in tumor samples, by polymerase chain reaction (PCR) on paraffin-embedded material., Results: Malignant transformation affects mainly men with a long-term history of genitoanal HS. Although our cases were 7 well-differentiated carcinomas and 6 verrucous carcinomas, lymphatic and visceral metastasis occurred in 2 and 3 cases, respectively. With PCR, we demonstrated presence of HPV in genitoanal tumoral lesions, principally HPV-16., Conclusion: SCC complicating HS evolves poorly, despite a good histological prognosis. Our results sustain the implication of HPV in the malignant transformation of HS.

Background: The role of chemotherapy in metastatic esophageal carcinoma (MEC) remains a matter of debate. The aim of this retrospective study was to analyze the survival impact of chemotherapy after stratification for prognostic factors., Methods: Consecutive patients with MEC (1995 to 2008) were randomly assigned to a development (n = 171) and a validation cohort (n = 113). We had first identified prognostic factors using the Kaplan-Meier and Cox methods in the development cohort and then validated them in the validation cohort. Then, we analyzed the impact of chemotherapy after stratification for these prognostic factors. The majority of patients had squamous cell carcinoma (80%)., Results: The Cox model has retained 2 prognostic factors only: associated cancers (hazard ratio = 2.77, range 1.39-5.54, p = 0.004) and grade 3-4 dysphagia (hazard ratio = 1.44, range 1.08-2.14, p = 0.007). Median survival was 10.9 in patients with 0 (n = 77), 6.2 in those with 1 (n = 65) and 1.8 months in those with 2 prognostic factors (n = 11/171; p = 0.025). The median survival times of the patients with 0, 1 and 2 prognostic factors were 13 versus 9 months (nonsignificant, NS), 6 versus 5 months (NS) and 5 versus 1.3 months (NS) in patients with and without chemotherapy, respectively., Conclusion: Our data suggest that chemotherapy has no significant effect on survival for unselected MEC patients, regardless of the prognostic factors we identified., (Copyright © 2010 S. Karger AG, Basel.)

Background: There is no international consensus on practical methods of monitoring melanoma following surgical removal of a primary tumour. The chief aim of such monitoring is to ensure detection of relapse where early diagnosis is crucial for survival (i.e. in-transit and lymph node metastases amenable to surgical removal) and the emergence of any first recurrence of primary melanoma., Aim: The aim of our study was to identify the role of various agents and diagnostic tools both in first recurrence of primary melanoma and in clinical relapse of melanoma., Patients and Methods: This was a retrospective study covering all patients with in-transit or regional lymph node metastasis seen between January 2005 and December 2007. The type of recurrence and method of detection were studied., Results: Ninety-four patients presented recurrence, with 66% of relapses comprising regional lymph node metastasis and 34% consisting of in-transit metastases. Thirty-three percent of cases of recurrence were detected by patients themselves, 21% by our department, 22% by a private dermatologist, 18% by a radiologist and 6% by a general practitioner. Fifty-four percent of recurrences among patients aged under 50 years were self-detected compared to 18% among patients aged over 70 years. A second melanoma was detected in six patients., Discussion: This study underscores the great importance of self-examination in melanoma follow-up with over one third of recurrences being self-detected by patients. Self-examination was more effective for younger patients, emphasizing the need to increase awareness among older patients. This study also demonstrates the essential part played by dermatologists in terms of regular follow-up of melanoma.

In June 2007, the CyberKnife has been implemented at Centre Oscar-Lambret in Lille. The program has been developed around specific clinical indications: head and neck reirradiation, liver. Early results are presented. The system includes several way of repositioning fixed targets and tracking moving targets with breathing. With each way, there is a dedicated tool for the quality control.

In the field of radiation oncology, equipment for fractionated radiotherapy and single-dose radiosurgery has become increasingly accurate, together with the introduction of robotized treatments. A robot is a device that can be programmed to carry out accurate, repeated and adjusted tasks in a given environment. Treatment of extracranial lesions involves taking into account organ mobility (tumor and healthy tissue) whilst retaining the ability to stereotactically locate the target. New imaging techniques (single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), positron emission tomography (PET)) provide further relevant information to slice images (computed tomography (CT) scans, MRI) for target definition. Hypo-fractionated treatments can only be used for curative treatment if the target is accurately defined and tracked during treatment. The CyberKnife is a non-invasive system of radiosurgery and fractionated stereotactic radiotherapy. For intracranial lesions treated by single-dose radiosurgery, it has been used to treat meningioma, acoustic neuromas, pituitary adenoma, metastases, arteriovenous malformations and refractory pain (trigeminal neuralgia). More than 10,000 patients have been treated worldwide. Currently, the most significant developments are in the field of extracranial stereotactic radiotherapy (lung, liver, reirradiation, prostate, etc.). Clinical results obtained in the CyberKnife Nord-Ouest program after 1 year of experience are presented., (Copyright 2009 S. Karger AG, Basel.)

We propose herein a review based on literature data about current treatment of Merkel cell carcinoma, including new data on adjuvant radiotherapy and sentinel lymph node biopsy.

Background and Purpose: The aim of this study was to prospectively assess the quality of life (QOL) of patients treated by concomitant chemo radiation for locally advanced anal canal carcinoma., Materials and Methods: We report on a subgroup of 119 patients enrolled in a 306-patient therapeutic intensification prospective trial (ACCORD 03). This trial evaluated the impact on colostomy-free survival of induction chemotherapy and/or high dose radiotherapy (factorial design 2 *2 treatment arms). QOL was assessed both before and 2 months after treatment using the EORTC QLQ-C30 questionnaire as well as a questionnaire relating to anal sphincter conservative treatment (AS-CT)., Results: Compared to pre-treatment scores, patients reported significant improvement in their emotional function (+8.4 points p=0.002), global health status (+5.9 points p=0.0007), as well as a decrease in insomnia (-13.8 points p<0.0001), constipation (-12.0 points p<0.0001), appetite loss (-10.3 points p<0.0001) and pain (-9.6 points p=0.0002). The AS-CT degree of satisfaction with intestinal functions score was increased (+11.2 points p<0.0001)., Conclusion: This is the first prospective study comparing QOL of patients with advanced anal canal carcinoma, before and 2 months after conservative treatment. Two months after treatment, QOL was improved. Induction chemotherapy and/or high dose radiotherapy did not provide a negative impact on QOL.

A phase I trial was initiated to establish the dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of chronomodulated 5-fluorouracil and cisplatin given concurrently with preoperative radiotherapy in patients with esophageal cancer. Patients with stage I or II esophageal cancer received preoperative radiation therapy (28-30 daily 1.8-Gy fractions for a total of 50.4 or 54 Gy) and concurrent three fortnightly cycles of chronomodulated 5-fluorouracil (700-835 mg/m2 per day, d1-d4, with peak delivery at 4.00 am) and cisplatin (50 mg/m2, d1, with peak delivery at 4.00 pm) administered by a time-programmable pump. Ten patients were treated on this study. Two of six patients treated at the starting dose-level experienced acute DLTs (esophagitis, asthenia) which required de-escalation of 5-fluorouracil. Five patients out of ten experienced seven DLTs (severe esophagitis, asthenia, vomiting: 5/1/1) at any dose-level. The MTD was not assessed because the study was halted due to slow accrual. Finally, two patients deceased from an Acute Respiratory Distress Syndrome due to inadequate radiation therapy planning. Without definitively ruling out any possible impact of chronomodulation in that setting, our data reinforce the need of a better selection of patients aimed to be treated by CRT plus surgery.

In 2006, 3 sites have been selected by the Institut national of cancer (Lille, Nancy et Nice) to evaluate a radiotherapy robot, the CyberKnife. This machine, able to track mobile tumours in real time, gives new possibilities in the field of extra cranial stereotactic radiotherapy. Functionalities and medico economical issues of the machine will be evaluated during 2 years on the 3 sites.

Purpose: The aim of this study was to retrospectively evaluate the feasibility, efficacy, and tolerance of external beam radiotherapy followed by high-dose-rate brachytherapy in inoperable patients with superficial esophageal cancer., Patients and Methods: From November 1992 to May 1999, 66 patients with superficial esophageal cancer were treated with exclusive radiotherapy. The median age was 60 years (range, 41-85). Fifty-three percent of them were ineligible for surgery owing to synchronous or previously treated head-and-neck cancer. Most of the patients (n = 49) were evaluated with endoscopic ultrasonography (EUS) or computed tomography (CT). The mean doses of external beam radiotherapy and high-dose rate brachytherapy were 57.1 Gy (+/-4.83) and 8.82 Gy (+/-3.98), respectively. The most frequently used regimen was 60 Gy followed by 7 Gy at 5 mm depth in two applications., Results: Among patients evaluated with EUS or CT, the complete response rate was 98%. The 3-, 5-, and 7-year survival rates were 57.9%, 35.6%, and 26.6%, respectively. Median overall survival was 3.8 years. The 5-year relapse-free survival and cause-specific survival were 54.6% and 76.9%. The 5-year overall, relapse-free, and cause-specific survival of the whole population of 66 patients was 33%, 53%, and 77%, respectively. Local failure occurred in 15 of 66 patients; 6 were treated with brachytherapy. Severe late toxicity (mostly esophageal stenosis) rated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale occurred in 6 of 66 patients (9%)., Conclusion: This well tolerated regimen may be a therapeutic alternative for inoperable patients with superficial esophageal cancer. Only a randomized study could be able to check the potential benefit of brachytherapy after external beam radiation in superficial esophageal cancer.

Background: Traditionally melanoma has been considered as a radioresistant tumor. However, recent observations regarding radiobiology and clinical response of melanoma have prompted physicians to re-evaluate the role of radiotherapy in the management of melanoma. Indeed, radiotherapy is frequently used in the treatment of metastatic melanoma but the role of this therapeutic approach in the primary tumor management is unclear. We report 4 cases of thick primary melanoma treated by interstitial brachytherapy., Case Reports: Four patients (3 men, 1 woman; age: 73, 74, 79, 84 years), three with lentigo maligna melanoma and one with nodular melanoma, were treated exclusively by interstitial brachytherapy. The thickness of the 4 tumors was more than 3 mm. This treatment was chosen either because of the impossibility of conservative surgery or because of a contraindication for general anesthesia. Median follow-up was 48 months [18 to 65 months] and we did not observe any local tumor relapse. The cosmetic and functional results of this therapy were excellent., Discussion: These four cases illustrate the possibility of obtaining good local control of thick primary melanoma by interstitial brachytherapy where surgery is impossible, although without challenging the standard surgical therapy for primary melanoma. Before our study, this treatment was used only in one study to treat melanoma patients. In this case however, interstitial brachytherapy was accompanied by surgery. Therefore, the findings reported here are the first to demonstrate the efficacy of this treatment when used as the sole treatment for primary melanoma. In conclusion, where surgery is difficult or impossible, interstitial brachytherapy may be used to treat primary melanoma with excellent local tumor control and a good cosmetic outcome.

Background: Photodynamic therapy is an endoscopic treatment of early cancers based on the photosensitisation of neoplasms following the administration of a photosensitiser prior to laser light-induced tissue destruction., Aim: To assess the results of photodynamic therapy using Photofrin(Axcan Pharma Inc., Quebec, Canada) in patients with an early oesophageal cancer., Patients: Twenty-four patients with early oesophageal cancer presenting as a not well-demarcated irregular dyschromic area of mucosa and unsuitable for any other treatment underwent photodynamic therapy. RESULTS.: Seventy-five per cent were successfully treated; three of them recurred and two died from head and neck cancer. To date, 54% of patients are alive without recurrence; the average follow-up is 21 months. There were one oesophageal lethal perforation and six stenosis. Results of photodynamic therapy were limited in this series by three failures, three recurrences and three deaths from previous head and neck cancers., Conclusion: This study provides some promising data for photodynamic therapy of oesophageal carcinomas in selected patients. It also emphasises the need for a best delivery device of laser light.

Background: Merkel cell carcinoma is a rare and potentially aggressive cancer of the skin. Cumulative data from small retrospective series have supported treatment by wide excision and adjuvant radiotherapy. However, wide excision may be difficult to perform in patients with tumors of the head and neck or in older populations with comorbidities that may be incompatible with general anesthesia., Observations: Nine patients (group 1) with stage I (without lymph node involvement) Merkel cell carcinoma primary tumors were treated in our center by radiotherapy alone. The rate of recurrence was compared between this group and 17 additional patients (group 2) with stage I Merkel cell carcinoma who received conventional treatment (surgery followed by radiotherapy)., Results: The median follow-up was 3.0 years (range, 8 months to 7 years) for group 1 and 4.6 years (range, 5 months to 11 years) for group 2. During this period, we observed 1 relapse and 1 progression of disease in group 2. No statistical difference was found in overall and disease-free survival between the 2 groups of patients., Conclusion: This study demonstrates the possibility of treating inoperable Merkel cell carcinoma by radiotherapy alone, with outcomes similar to those of classic treatment.

Little is known about epidemiology of adults soft tissue and visceral sarcomas (ASTS). The frequency of previous cancers and associated genetic diseases has been analyzed out of 493 ASTS, treated between 1997 and 2002 at Oscar Lambret Cancer Center. Median age is 51, sex ratio is close to 1. Liposarcomas and malignant fibrous histiocytofibromas are the two main types (respectively 104 and 86 cases). Upper and lower limbs are the two main locations (respectively 176 and 75 cases). Fifteen patients had associated genetic disease, including 12 cases of Recklinghausen diseases. 7 out of those 15 patients have neurosarcoma. 30 patients have previous cancers, including 7 breast cancers, 3 lymphomas and 3 chronic lymphocytic leukemias. Four out of those 30 patients have two different previous cancers. 13 patients have radiation-induced sarcomas, after an average 10-year-period, and an average dose of 53 Gy. Undifferenciated sarcomas are the main histologic type (8/13), followed by angiosarcomas (2/13). Radiation-induced sarcomas are located in the chest wall (7/13), in pelvis (2/13) and head and neck (2/13). Those sarcomas are high grade (10 grade III tumours). ASTS epidemiology is complex with different risk factors depending on histologic type.

The aim of this work, synthesized from personal case reports and a review of literature is to describe cutaneous complications of radiation therapy (except radiation-induced cancers): known and frequent such as radiation dermatitis or less frequent, beginning or strictly limited on irradiated skin areas: acne, infectious diseases, dyskeratosis, Grover's disease, sub-cutaneous pustulosis, cutaneous lichen, morphea, autoimmune bullous dermatosis, subacute cutaneous lupus erythematosus. Furthermore, we try to precise the physiopathogenic mechanisms of these dermatosis and we want to draw the attention on these dermatoses which sometimes need a multidisciplinary approach.

Introduction: Primitive cutaneous neuroendocrine carcinoma (PCNC) is a rare tumor with poor prognosis. Surgery is the treatment of choice, but radiotherapy is taking a larger place in the management of these patients., Methods: The files of 22 patients were studied retrospectively over a period of 14 years., Results: The study included 17 women and 5 men with a mean age of 75.5 years. The localization of the tumor was the cephalic extremity in 12 cases. At the initial stage, the tumor in 3 of the 22 patients was of glandular or visceral localization. Thirteen stage I patients were treated surgically. Adjuvant radiotherapy was performed in 10 of these patients and only one relapsed (incomplete initial exeresis). The other three relapsed. Exclusive radiotherapy led to complete response in 4 patients who could not undergo surgery and in 2 with local relapses. Seven patients exhibited glandular involvement and 6 of them died (median 7 months) after the adenopathy had been discovered., Discussion: Our series illustrates the clinical characteristics of this tumor of the elderly, which is predominantly cephalic and of rapid progression. From a therapeutic point of view, our results underline the benefit of radiotherapy as adjuvant to surgery. When surgery is impossible, and in the case of local relapse, radiotherapy gives good results.

Although slightly declining in France, the incidence rate of esophageal cancer remains amongst the highest seen in Europe, especially in Brittany, in the North as well as in Normandy. Alcohol and tobacco consumption remains the main risk factor for esophageal cancer in Western countries. Positive diagnosis of esophageal cancer is made by upper gastrointestinal endoscopy combined with biopsies. At present, surgery and definitive radiochemotherapy are two therapeutic options offering a chance to cure even though surgery remains the more frequently used treatment. Five-year-survival rate after apparently curative surgical resection or definitive radiochemotherapy remains only 20% in most population-based series. The studies that have examined the role of adjuvant treatments after surgical resection, have failed to demonstrate any improvement in overall or relapse-free survival. The pre-operative cytotoxic combined modality approaches with radiochemotherapy have shown improved relapse-free survival but still remains experimental. Finally, the symptomatic treatment of dysphagia might not be ignored either in locally, locally advanced, or in metastatic disease.

Purpose: To analyse toxicity and response to a new scheme of neoadjuvant chemotherapy (CT) and concomitant radiochemotherapy (RT-CT) for locally advanced anal canal squamous-cell carcinoma (ACC)., Patients and Methods: Eighty patients with an ACC > 40 mm and/or with lymph node involvement were included (1 T1, 52 T2, 14 T3, 13 T4, 18 N0, 30 N1, 32 N2-N3). Two cycles of 5-fluorouracil (5-FU) and CDDP were delivered as neoadjuvant CT and two during RT-CT. Pelvic (+/- inguinal) RT delivered 45 Gy in 25 fractions of 1.8 Gy. Involved fields were boosted after a one to two month gap (15-20 Gy). The median follow-up was 29 months., Results: One patient died of a pulmonary embolism on day 4. All patients received the entire treatment, with reduced 5-FU doses in 27% of the cases because of acute toxicity. Sixty-four grade 3 and five grade 4 toxicities were observed. No toxic death occurred. Complete response (CR) and partial response (PR) rates were, respectively, 10% and 51% after neoadjuvant CT, 67% and 28% after RT-CT and 93% and 5% after treatment completion (including 4 abdomino-perineal resections). The three-year actuarial overall, tumour-specific, colostomy-free, relapse-free, disease-free and event-free survivals were 86%, 88%, 73%, 70%, 67% and 63%, respectively., Conclusions: Tolerance was good. After neoadjuvant CT, most of the patients were objective responders. After treatment completion, all but five achieved CR. The long-term results confirm the durability of local control and low toxicity on the sphincter. An ongoing phase III intergroup trial analyses the impact of neoadjuvant CT, and the benefit of a high-dose boost irradiation, on local control and colostomy-free survival.

Purpose: Retrospective analysis of the results obtained with daily interactive use of portal imaging for monitoring thoracic cancer radiotherapy., Materials and Methods: A Siemens electronic portal imaging system called Beamviewplus was used daily in 15 lung cancer patients for each X-ray field. Out of the 714 expected portal images, 585 (82%), were obtained and printed., Results: We counted 94 errors in the 585 successful controls (16%). Four main classes of errors were identified: irradiation field placement (47 cases, 50%), shielding placement (30 cases, 32%) patient's position on the till examining table (14 cases, 15%), and selection of the energy (3 cases, 3%). Forty percent of these errors were potentially serious in terms of treatment volume and vital organ protection., Conclusion: Only portal imaging control could easily detect errors because they occurred randomly. We thus consider the use of this daily system helpful for patient management.

Purpose: Thymoma is a rare disease. The treatment of patients with invasive thymoma remains controversial. The prognosis of such patients is poor, even with the use of postoperative radiation therapy and chemotherapy. We retrospectively reviewed the outcome and prognostic factors in a series of 90 patients presenting with an invasive thymoma treated by partial resection or biopsy and radiation therapy., Methods and Materials: From 1979-1990, 163 patients with the diagnosis of lymphoepithelial thymoma were treated in 10 French cancer centers. Patients were staged using the postoperative "GETT" classification derived from that of Masaoka. Ninety patients who presented with an invasive thymoma, 58 Stage III (21 IIIA: partial resection and 37 IIIB: biopsy) and 32 Stage IVA (intrathoracic thymoma spread), are the subject of this report. Treatment combined surgery and radiation therapy (+/- chemotherapy), with curative intent. Surgery consisted of partial resection in 31 patients (21 Stage III), and biopsy in 55 patients (37 Stage III). The median radiation dose to the tumor was 50 Gy (30-70 Gy). Supraclavicular radiation was performed in 59 patients (median dose 40 Gy). Chemotherapy, combined with radiation in 59 patients, consisted of multidrug regimens, mainly platinum based., Results: The median follow-up is 105 months (20-165 months). The 5- and 10-year overall survival rates are 51 and 39%, respectively. There is a great impact of the extent of surgery on survival: the 5- and 10-year survival rates were 64% and 43%, respectively, after partial resection, compared to 39% and 31% after biopsy (p < 0.02). Local control at 8.5 years was obtained in 59 of 90 patients (66%): 40 Stage III, 19 Stage IVA. There is a significant relationship between the extent of surgery and the local control (16% of relapse after partial resection vs. 45% after biopsy, p < 0.05). Seven patients developed significant (grades 3-4 WHO grading system) treatment-induced side effects. Stage, histologic type, and chemotherapy were not prognostic factors., Conclusion: In this large multicentric retrospective study of invasive thymomas (Stage III-IVA) treated by surgery and radiation, results show the importance of loco-regional treatments, such as surgery and radiation therapy. There is also a great impact of radiation on local control. However, the rate of local recurrence (34%) justifies recommending a higher dose of radiation (> 50 Gy) than doses used in this study, for incompletely resected patients. The role of chemotherapy needs to be further assessed.

Thymomas is a rare disease. Staging systems and surgical adjuvant treatments remain controversial. We retrospectively reviewed the outcome and the prognostic factors in a series of 149 patients with non metastatic thymomas treated in ten French cancer centers between 1979 and 1990. Patients were staged according to the "GETT" classification derived from that of Masaoka. There were 13 stage I patients, 46 stage II, 58 stage III and 32 stage IV. Surgery consisted of complete resection in 63 patients, partial resection in 31 patients and biopsy alone in 55 patients. All patients received postoperative radiation therapy and 74 were given postoperative chemotherapy. Median follow-up was 7.7 years. Local control was obtained in 117 patients (78.5%) and was influenced by the extent of surgery (p < 0.0001). Metastases occurred in 26 patients. Seven patients developed grade 3-4 pulmonary and heart complications. One patient developed a malignant lymphoma after 24 cycles of chemotherapy. Disease-free survival (DFS) rates were of five years 92%, 75%, 60%, 39% and 48% in stage I, II, IIIA, IIIB and IVA patients, respectively. After complete resection, partial resection and biopsy alone, these rates were 74%, 60% and 38%, respectively. With a multivariate analysis, DFS rates were influenced by the extent of surgery (p < 0.001) and by chemotherapy (p < 0.001). Three other factors could predict a worse DFS: young age (p < 0.006), stages III-IV (p < 0.04) and mediastinal symptoms (p < 0.001), "GETT" staging correlated well with local control and survival. After complete resection, a 50 Gy postoperative radiation therapy can be recommended in patients with invasive thymomas. Despite a 65% local control rate after partial resection or biopsy alone in this series, a higher dose of radiation (> 60 Gy) must be evaluated. Despite the benefit of the chemotherapy in this retrospective and multicentric study, the role of this treatment remains to be assessed.

From 1974 to 1983, 579 patients presenting with early oral cancer (excluding lip tumours) were treated at Centre Oscar Lambret. Of these, 429 were treated locally by brachytherapy with local control achieved in 82% of the cases (90% after salvage surgery). Treatment-related complications occurred in 19% of the cases, requiring surgical management in 13 patients. In contrast, only 51% of the 35 patients treated by external radiotherapy and brachytherapy were controlled, resulting in a poor 5-year survival (14%). Results for the 24 patients treated surgically were similar to those of brachytherapy alone. Finally, for T1 T2 N0 patients, the advantages of an elective neck dissection are not clear and could be clarified by a randomised trial. Indeed, this retrospective study failed to find a significant difference in the incidence of death due to an uncontrolled neck evolution whatever the neck management.

A prospective comparative study of the alveolar bone resorption after teeth extraction was achieved in a series of 79 patients in order to analyze macroscopically the possible consequences of radiotherapy and chemotherapy on the toothless edges. After quarterly coronal and sagittal X-rays for two years, this study enhances quite a similar vertical resorption for the radiation and chemotherapy-treated patients as well as for the witness patients. The alveolar bone resorption progression also appears unaltered by anti cancerous treatments. In both cases, a resorption stabilisation can be clearly seen after 6 months according to dental extractions. The vertical alveolar bone resorption is more important in incisor and canine regions. The anti cancerous treatments may not have significant disastrous consequences as far as available bone amount is concerned, on a post prosthetic restoration.