[Place of radiotherapy in the treatment of cutaneous carcinomas]. / Place de la radiothérapie dans le traitement des carcinomes cutanés.

Basal cell carcinomas and cutaneous squamous cell carcinomas are among the most common cancerous tumors in the world. Their treatment is most often based on surgery. Adjuvant radiotherapy may be indicated in case of risk factors for recurrence or as an alternative to surgery if surgery is not feasible due to the patient's advanced age and/or co-morbidities or as an alternative to potentially mutilating surgery. Radiotherapy is also part of the therapeutic arsenal for rarer skin tumors such as Merkel cell carcinoma, cutaneous lymphomas, Kaposi's disease and cutaneous adnexal carcinomas.

Evaluation of adjuvant vaginal vault brachytherapy in early stage cervical cancer patients.

PURPOSE: Adjuvant external beam radiotherapy (EBRT) was shown to decrease pelvic relapses in patients with an early stage cervical cancer and intermediate-risk histopathological prognostic factors, at the cost of increased bowel morbidity. We examined the feasibility and results of adjuvant brachytherapy alone as an alternative to EBRT in this situation. PATIENTS AND METHODS: Medical records of consecutive patients receiving adjuvant brachytherapy between 1991 and 2018 for an early stage cervical cancer were examined. Patients were included if they presented a pT1a2N0 or pT1b1N0 disease following radical colpohysterectomy. Adjuvant vaginal wall brachytherapy (without EBRT) was indicated because of a tumor size≥2cm and/or presence of lymphovascular space invasion (LVSI). Patients received 60Gy to 5mm of the vaginal wall, through low-dose or pulse-dose rate technique. Patients' outcome was examined for disease control, toxicities and prognostic factors. RESULTS: A total of 40 patients were included. Eight patients (20%) had LVSI, 26 patients (65%) had a tumor size≥2cm. With median follow-up time of 42.0 months, 90% of patients were in complete remission and four patients (10%) experienced tumor relapse, all in the peritoneal cavity, and associated with synchronous pelvic lymph node failure in 2/4 patients. No vaginal or isolated pelvic nodal failure was reported. At 5 year, overall survival was 83.6% (CI95%: 67.8-100%) and disease-free survival was 85.1% (CI95%: 72.6-99.9%). In univariate analysis, probability of relapse correlated with tumor size≥3cm (P=0.004). No acute or late toxicity grade more than 2 was reported. CONCLUSION: Brachytherapy alone was a well-tolerated adjuvant treatment for selected patients with intermediate risk factors. The risk of relapse in patients with tumor size≥3cm was however high, suggesting that EBRT is more appropriate in this situation.

Implementation of image-guided brachytherapy as part of non-surgical treatment in inoperable endometrial cancer patients.

OBJECTIVE: This study assessed outcomes of inoperable endometrial cancer (IEC) patients treated with definitive external beam radiation therapy (EBRT) followed by a 3D image-guided brachytherapy boost. METHODS: All consecutive patients treated with EBRT followed by 3D image-guided brachytherapy for IEC were retrospectively included. EBRT delivered a dose of 45Gy. Then, patients had an uterovaginal brachytherapy guided by 3D imaging. Clinical target volume (CTVBT) included the whole uterus and the initial disease extent. Gross tumour volume (GTVres) included the residual disease at time of brachytherapy. RESULTS: Twenty-seven patients were identified. Causes of inoperability were comorbidities (37%) or tumour loco regional extent (63%). Including EBRT and brachytherapy, the median D90 (minimal dose delivered to 90% of the volume) was 60.7 GyEQD2 (IQR = 56.4-64.2) for the CTVBT, and was 73.6 GyEQD2 (IQR = 64.1-83.7) for the GTVres. The median overall treatment time was 50 days (IQR = 46-54). The mean follow-up was 36.5 months (SD = 30.2). The cumulative incidence of local, pelvic and distant failures was 19% (n = 5), 7% (n = 2) and 26% (n = 7), respectively. Five-year overall survival was 63% (95% CI = 43-91). Late urinary and gastro intestinal toxicities ≥ grade 2 were reported in four (15%) and two patients (7%) respectively. No vaginal toxicity ≥ grade 2 was reported. CONCLUSIONS: EBRT followed by intracavitary brachytherapy seems to be an effective option for IEC. The implementation of 3D concepts at time of brachytherapy may contribute to high local control probability and low toxicity profile. Large scale retrospective or prospective data are needed to confirm these early data.

Comprehensive analysis of patient outcome after local recurrence of locally advanced cervical cancer treated with concomitant chemoradiation and image-guided adaptive brachytherapy.

INTRODUCTION: Since dose escalation allowed by image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer (LACC), local relapses have become a rare event. Only scarce data are available on the outcome of patients experiencing a local relapse after IGABT. METHODS: Between 2004 and 2016, all consecutive patients treated at Gustave Roussy Institute for LACC and receiving concomitant chemoradiation and IGABT were analysed. Clinical and treatment-related prognostic factors for survival after local relapse were searched, in order to potentially identify patients requiring salvage treatment. RESULTS: Two hundred and fifty-nine patients were treated during this period. With a median follow-up of 4.1 years, 10.8% (n = 28) had a local relapse. Among these patients, 53.6% had synchronous lymph nodes or distant metastatic relapse and only 13 patients (5% of all patients) had isolated local relapse. After local relapse, median survival was 47 months and three patients were alive at last follow-up. Only three patients with local relapse could receive salvage surgery (10.7%). Metastases occurrence and pelvic wall involvement were the main contraindications (67.9%) for salvage surgery. Among the three patients treated with surgery, two are still alive at last follow-up without significant complication. Improved survival was observed among the two patients who could have surgery (p = .02). Local progression led to serious symptoms in 75% of patients. Only the time interval between brachytherapy and relapse (<1 year) was prognostic for 2-year overall survival (p = .005). CONCLUSION: Salvage surgery is feasible in a very low number of highly selected patients with local relapse following IGABT. Local failure is a major cause of severe local symptoms, confirming that every effort should be done to achieve long-term local control through dose escalation.

Correlation between pelvic bone marrow radiation dose and acute hematological toxicity in cervical cancer patients treated with concurrent chemoradiation.

PURPOSE: To evaluate the association between pelvic bone marrow (BM) dose volume parameters and probability of acute hematological toxicity (HT), a cohort of cervical cancer patients receiving definitive chemoradiation (CRT) was assessed. MATERIALS AND METHODS: Medical records of patients treated by CRT (45 Gy in 25 fractions, without dose constraints applied to the BM) were reviewed. Baseline and weekly hematological parameters were collected. BM was retrospectively delineated and divided into sub-sites: iliac crests, lower pelvis, lumbosacral region. BM volumes (V) receiving 5, 10, 20, 30, 40 Gy (V5, V10, V20, V30, V40, respectively) and mean dose (Dm) were calculated. Logistic regression was used to analyze associations between HT and dose-volume histograms parameters. RESULTS: 114 patients were included. 75.4% were treated with 3D radiation therapy and 24.6% were receiving intensity modulated radiation therapy (IMRT). Neither age, chemotherapy regimen (cisplatin vs carboplatin), number of chemotherapy cycles, performance status, body mass index, or para-aortic irradiation were associated with HT. In univariate analysis, more frequent grade 3+ leukopenia was found in the IMRT group (odds ratio [OR]: 3.5; 95% CI, 1.4-9.1; p=0.007). In multivariate analysis, grade 4 HT was associated with lower pelvis V5>95% (OR 4.1; 95% CI, 1.6-14. p=0.02), lower pelvis V20>45% (OR 3.5; 95% CI, 1.1-13.4; p=0.05), total pelvic bone V20>65%, and iliac crests Dm >31 Gy (OR 4.5; 95% CI, 1.4-14.7; p=0.02). CONCLUSION: The following dose constraints could be proposed to decrease acute HT risk: lower pelvis V5<95%, lower pelvis V20≤45%, total pelvic bone V20<65%, and iliac crests Dm <31 Gy.

Anti-PD-1 immunotherapy in combination with sequential involved-site radiotherapy in heavily pretreated refractory Hodgkin lymphoma.

The purpose of this study was to assess efficacy and tolerance of anti-programmed death (PD)-1 immunotherapy in combination with sequential involved-site radiotherapy in heavily pretreated refractory Hodgkin lymphoma. In this case series, we reported the outcome of four heavily pretreated patients with refractory Hodgkin lymphoma treated by anti-PD-1 immunotherapy and involved site radiation therapy. After a median follow-up of 13-month, all patients were alive with complete metabolic response. After radiotherapy, all four patients experienced lung toxicity, which was resolved after antibiotherapy with or without corticosteroid treatment. Anti-PD-1 immunotherapy followed by involved-site radiotherapy is feasible and showed very encouraging results in heavily pretreated patients.

[Siriade 2.0: An e-learning platform for radiation oncology contouring]. / Siriade 2.0 : outil de formation en ligne à la délinéation en radiothérapie.

PURPOSE: In 2008, the French national society of radiation oncology (SFRO) and the association for radiation oncology continued education (AFCOR) created Siriade, an e-learning website dedicated to contouring. MATERIAL AND METHODS: Between 2015 and 2017, this platform was updated using the latest digital online tools available. Two main sections were needed: a theoretical part and another section of online workshops. RESULTS: Teaching courses are available as online commented videos, available on demand. The practical section of the website is an online contouring workshop that automatically generates a report quantifying the quality of the user's delineation compared with the experts'. CONCLUSION: Siriade 2.0 is an innovating digital tool for radiation oncology initial and continuous education.

[Why is brachytherapy still essential in 2017?] / Pourquoi la curiethérapie reste-t-elle indispensable en 2017 ?

These recent years, brachytherapy has benefited from imaging modalities advances. A more systematic use of tomodensitometric, ultrasonographic and MRI images during brachytherapy procedures has allowed an improvement in target and organs at risk assessment as well as their relationship with the applicators. New concepts integrating tumor regression during treatment have been defined and have been clinically validated. New applicators have been developed and are commercially available. Optimization processes have been developed, integrating hypofractionation modalities leading to tumor control improvement. All these opportunities led to further development of brachytherapy, with indisputable ballistic advantages, especially compared to external irradiation.

3D brachytherapy for cervical cancer: New optimization ways.

Brachytherapy has known major improvements in recent decades. It represents an essential component of local treatment of cervix cancers. One major breakthrough was the advent of 3D imaging for image-guided brachytherapy. Doses could be prescribed to volumes. This allows better delineation and coverage of target volumes, as well as organs at risk (bladder, rectum, sigmoid) protection. Local recurrences have been consequently reduced and survival has been improved. In addition, improvement and development of new applicators have facilitated the delivery of interstitial treatments. Afterloading applicators, associated with 3D imaging, allow dosimetry optimization in order to improve the coverage of the target volumes (dose in 90% of the high risk clinical target volume) and to limit dose to the organs at risk. In the future, more personalized treatments will be achieved through more advanced applicators and/or by improving the accuracy of imaging at the time of brachytherapy.

[Combination of radiotherapy and androgen deprivation therapy for localized prostate cancer]. / Associations d'hormonothérapie et de radiothérapie pour le cancer de prostate.

Combination of radiotherapy and androgen deprivation is now considered as the standard of care for patients with a localized prostate cancer but poor prognosis factors. Two groups of randomized trials have led to this recommendation: some have compared radiotherapy alone versus hormonal treatment and radiotherapy: these trials demonstrated, now with a long follow-up, an improvement in 10-year survival for the combined treatment. Three recent trials compared androgen deprivation alone or combined with radiotherapy; a benefit in survival was also demonstrated in favour of the combination. Some questions remained concerning the optimal duration of hormonal treatment, in view of its potential side effects. Patients in the intermediate prognostic groups could receive a short-term androgen deprivation, but those with a high Gleason score must be treated with a long-term hormonal treatment. Modalities of radiotherapy, regarding volumes and dose must also be précised in the next years.

[Stereotactic radiotherapy for pelvic tumors]. / Place de la radiothérapie en condition stéréotaxique dans la prise en charge des tumeurs pelviennes.

Extracranial stereotactic radiotherapy is booming. The development and spread of dedicated accelerators coupled with efficient methods of repositioning can now allow treatments of mobile lesions with moderate size, with high doses per fraction. Intuitively, except for the prostate, pelvic tumours, often requiring irradiation of regional lymph node drainage, lend little to this type of treatment. However, in some difficult circumstances, such as boost or re-radiation, stereotactic irradiation condition is promising and clinical experiences have already been reported.

[Brachytherapy training: a survey of French radiation oncology residents]. / État des lieux de la formation des internes français d'oncologie radiothérapie en curiethérapie.

PURPOSE: The goal of this study was to evaluate the interest of the members of the French society of young radiation oncologists (SFjRO) for brachytherapy as well as their theoretical and practical level in this radiation technique. MATERIALS AND METHODS: An anonymous survey was conducted regarding practical and theoretical teaching of brachytherapy before the French national courses on brachytherapy. RESULTS: Among the 106 residents attending this teaching course, 99 (93%) answered the survey. Most of them were interested in brachytherapy but 82% considered they had not received sufficient teaching. Relevant indications of brachytherapy were known by 76% of the residents for gynaecological malignancies and 70% for prostate. Seventy-one percent of the residents have seen at least one gynecological brachytherapy but only 12% knew how to deal with this technique. Fifty-six percent have seen vaginal high dose rate brachytherapy and 21% had acquired the technique. For prostate brachytherapy, 65% had seen and done an implant and only 4% had acquired the technique. Fifty percent have performed at least one brachytherapy treatment during their residency. Residents expressed a strong wish for more courses about dosimetry (82%), technique (75%) and treatment planning (90%). CONCLUSION: Our study shows the interest of French residents for brachytherapy but suggests that practical teaching courses and an evaluation of the existing theoretical courses are warranted.

Delegation of medical tasks in French radiation oncology departments: current situation and impact on residents' training.

OBJECTIVES: A national survey was conducted among the radiation oncology residents about their clinical activities and responsibilities. The aim was to evaluate the clinical workload and to assess how medical tasks are delegated and supervised. MATERIALS AND METHODS: A first questionnaire was administered to radiation oncology residents during a national course. A second questionnaire was mailed to 59 heads of departments. RESULTS: The response rate was 62% for radiation oncology residents (99 questionnaires) and 51% for heads of department (30). Eighteen heads of department (64%) declared having written specifications describing the residents' clinical tasks and roles, while only 31 radiation oncology residents (34%) knew about such a document (P=0.009). A majority of residents were satisfied with the amount of medical tasks that were delegated to them. Older residents complained about insufficient exposure to new patient's consultation, treatment planning and portal images validation. The variations observed between departments may induce heterogeneous trainings and should be addressed specifically. CONCLUSION: National specifications are necessary to reduce heterogeneities in training, and to insure that the residents' training covers all the professional skills required to practice radiation oncology. A frame endorsed by academic and professional societies would also clarify the responsibilities of both residents and seniors.

[Stereotactic body radiation therapy for liver primary and metastases: the Lille experience]. / Radiothérapie stéréotaxique hépatique par CyberKnife(®) : l'expérience lilloise.

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).

Endoscopic evaluation of the effects of indobufen and aspirin in healthy volunteers.

This is an outcomes pharmacodynamic study using Nonsteroidal antiinflammatory agents, particularly acetylsalicylic acid (ASA), have been shown useful in various cardiovascular disorders, but they can be a major cause of iatrogenic gastrointestinal injury. Newer NSAIDs such as indobufen, an inhibitor of platelet aggregation that acts by reversibly inhibiting the platelet cyclooxygenase enzyme, have proven to be as effective as the older NSAIDs and appear to have a better gastrointestinal tolerability profile. When the gastroduodenal tolerability of 10 days of oral treatment with indobufen or ASA was assessed in healthy adult volunteers using endoscopic evaluation and the modified score scale of Lanza, only 1 of 18 (6%) volunteers who received indobufen had an increased erosion score at the completion of therapy, compared with 6 of 18 volunteers who received ASA (33%). Overall, both drugs were well tolerated. These results suggest that indobufen has a lower incidence of gastrointestinal effects than other NSAIDs and should be useful in the management of patients with cardiovascular disease.

Comparable efficacy of pantoprazole and omeprazole in patients with moderate to severe reflux esophagitis. Results of a multinational study.

AIM: To compare the efficacy and tolerability of pantoprazole 40 mg and omeprazole MUPS 40 mg in patients with moderate to severe gastroesophageal reflux disease (GERD). METHODS: In this randomized, double-blind, parallel-group, multicenter study conducted in Austria, Germany, Portugal, Switzerland and The Netherlands, patients with endoscopically confirmed moderate to severe GERD (Savary/Miller esophagitis grade II/III) were enrolled. They received a once-daily dose of either 40 mg pantoprazole or 40 mg omeprazole MUPS. Healing was determined by endoscopy after 4 weeks of treatment. If patients were not healed, treatment was extended for another 4 weeks. An additional endoscopy was performed in these cases after 8 weeks of treatment. Healing was determined by endoscopy after 4 and 8 weeks. In addition, treatment effect on symptoms was evaluated by the investigator using a questionnaire assessing heartburn, reflux regurgitation and pain on swallowing at each visit, as well as by a self-administered questionnaire comprising further 24 gastrointestinal symptoms. Analyses were performed for the intention-to-treat (ITT) and the per-protocol (PP) population. In addition, patients with high compliance (HC: 90%

Effect of cisapride on relapse of esophagitis. A multinational, placebo-controlled trial in patients healed with an antisecretory drug. The Italian Eurocis Trialists.

The effect of a prokinetic agent, cisapride, on the relapse of reflux esophagitis was investigated in a randomized, double-blind trial conducted in 443 patients whose esophagitis had previously been healed with an acid antisecretory drug. Patients received cisapride, 20 mg at night, cisapride 10 mg twice daily, or placebo for 12 months or until endoscopic relapse was confirmed endoscopically. In 88% of all patients (respectively 133, 132, and 124), endoscopic data were available at discontinuation of treatment. In comparison with placebo, the two cisapride regimens prolonged both the time to endoscopically confirmed relapse (Kaplan-Meier analysis; P = 0.001) and the time to symptomatic relapse (P = 0.012). The life-table endoscopic relapse rates at 12 months were 51% for placebo, 32% for cisapride 20 mg at night (P = 0.005), and 34% for cisapride 10 mg twice daily (P = 0.02). Patients with more severe esophagitis before healing relapsed more rapidly during maintenance therapy, regardless of the treatment regimen. Adverse events were infrequent in all three groups. These findings indicate that maintenance treatment with the prokinetic drug cisapride prevents the relapse of esophagitis after it has been healed by acid antisecretory therapy.

Gastric ulcer: a double blind comparison of 800 mcg misoprostol versus 300 mg ranitidine.

Seventy-nine patients with endoscopically confirmed gastric ulcers received either ranitidine (37 patients) or misoprostol (42 patients) in a randomized double-blind manner. Fifty-six percent of the patients treated with ranitidine, and 38% of those treated with misoprostol presented with endoscopically healed ulcers after four weeks of treatment. After eight weeks complete healing had occurred in 86% of the patients receiving ranitidine, and 74% of those on misoprostol. These differences were not statistically significant. In smokers, ranitidine was superior to misoprostol, leading to a higher healing rate at four weeks (73% versus 20%). Thus there was no evidence that in patients with gastric ulcer misoprostol overcomes the negative effect of cigarette smoking.

Presenting characteristics of patients with duodenal ulcer and outcome of medical treatment in controlled clinical trials using cimetidine and diethylamine persilate to treat ulcer attack and diethylamine persilate and placebo to prevent relapses.

A double-blind controlled clinical trial on the medical treatment of the acute episode of duodenal ulcer and the prevention of symptomatic relapses was performed. A total of 164 patients with active duodenal ulcer were either treated with cimetidine 1 g/day (70 patients), diethylaminepersilate (DAP) 1.5 g/day (64 patients) or DAP 2.5 g/day (30 patients). DAP is an allegedly protective agent stimulating mucosal prostaglandin synthesis. Cumulative healing rates after 4 weeks in the 3 groups were 66, 28 and 28% and after 8 weeks 94, 70 and 63%, respectively. One hundred and five patients with healed duodenal ulcer received, in a second double-blind study, either DAP 0.5 g/day or placebo. Thus, ulcer healing was more rapid with cimetidine than with DAP. DAP did not prevent relapses. No presenting characteristic was associated with slow healing. Three presenting characteristics--smoking, teetotalling and bleeding episode in the past--were associated with early symptomatic relapse. The present study was compared with a previous study performed by the same group of investigators using a similar study protocol. In both trials, an early relapse was associated with smoking. No other presenting characteristic was identified which in both trials was associated with slow healing or early symptomatic relapse. Thus, smoking appears to be the only one of the commonly available presenting characteristics which allows a prediction of the course of duodenal ulcer disease.

Healing and relapse of reflux esophagitis during treatment with ranitidine.

In 108 patients the healing and relapse of reflux esophagitis, defined endoscopically by the presence of epithelial defects (erosions and ulcerations) of the esophageal mucosa, were studied. In the first study, with open treatment of ranitidine, the healing rate after 6 wk was 50%. The most important factor that negatively influenced healing was the extent of esophageal erosions. Patients with isolated erosions had a 6-wk healing rate of 78%; the healing rate was 38% in patients with longitudinally confluent lesions and 23% in those with circumferential erosions of the distal esophagus. Smoking also had an unfavorable effect. Age, sex, duration of history, body weight, and alcohol consumption were not related to outcome. Symptoms improved during treatment with ranitidine, but the correlation between symptoms and endoscopic findings at 6 wk was weak. In the second study, relapse was investigated in 61 patients with healed esophagitis in a randomized, double-blind trial comparing placebo and ranitidine (150 mg at bedtime for 6 mo). In both groups, relapse occurred in more than one-third of the patients, with no significant difference between ranitidine and placebo treatment. Patients with worse daytime symptoms at the time of previous healing had a higher relapse rate. The initial severity of esophagitis and smoking did not influence recurrence. Thus, the initial endoscopic findings are of prognostic value in reflux esophagitis. Smoking retards healing. Low-dose maintenance treatment with ranitidine does not prevent relapse.