Tolerance and efficacy of dose escalation using IMRT combined with chemotherapy for unresectable esophageal carcinoma: Long-term results of 51 patients.

PURPOSE: The optimal dose in esophageal cancer patients treated with definitive chemoradiation (CRT) remains debated. We herein report on the dosimetric results, treatment-related toxicities and long-term outcomes of escalated dose up to 60Gy delivered with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: All consecutive patients that received a definitive CRT>50Gy for an unresectable esophageal carcinoma between 2010 and 2015 were retrospectively evaluated for this study. Methodology included data base search, delayed toxicity grading, statistical testing including frequency analysis and survival analysis. RESULTS: A total of 51 patients were irradiated for a squamous cell carcinoma (86.3%) or an adenocarcinoma (13.7%). The median age at diagnosis was 62 years. Seven patients were simultaneously irradiated for another synchronous primary tumor. Forty-six patients (90.2%) received concurrent platin-based chemotherapy. The median prescribed doses were 60Gy (54-66) and 48Gy (44.8-56) delivered in 30 (27-35) fractions to the high and the low risks PTV respectively. The mean dose delivered to the lungs was 11.4Gy (IC 95%: 4.8-19.8), the median volumes receiving up to 20Gy (V20) and 30Gy (V30) were 13.5% (3.0-46.0) and 4.6% (0.7-19.8) respectively. The mean dose delivered to the heart was 13.9Gy (IC 95%:0.3-31.3) with a median V40 of 3.3% (0.0-25.0). One treatment-related death occurred within days after RT completion (neutropenic aplasia). After a median follow-up of 2.7 years (95% CI: 1.9-4.3), the 2-year overall survival, disease free survival and loco-regional control rates were 53.6%, 42.0% and 72.8% respectively. Delayed treatment related-toxicities ≤grade 3 occurred among 25 patients (62.5%) mostly esophageal stricture (79.2%). CONCLUSION: We demonstrated in this study that dose escalation using IMRT in combination with platin-based chemotherapy as a definitive treatment for esophageal carcinoma is safe and results in higher loco-regional and control survival when compared to previously reported data.

[Rib fracture following intra-operative radiotherapy for breast cancer. Case Report and local experience]. / Fracture de côte suite à la radiothérapie peropératoire dans le cancer du sein. Cas clinique et expérience locale.

Intra-operative radiotherapy for breast cancer has been developed throughout the last two decades. It is already well-established regarding local control and toxicity for intra-operative radiotherapy using electrons as we now have the necessary background knowledge. However, very few data on later toxicity are available for intra-operative radiotherapy using low-energy photons. We report here the case of a 36-year-old woman who experienced rib fracture following intra-operative and external radiotherapy. This patient has been included in the Targit-boost trial. The intra-operative irradiation has been operated with an INTRABEAM device delivering low-energy photons of 50-kV.

[Stereotactic hypofractionated radiation therapy as a bridge to transplantation for hepatocellular carcinoma: Case report of a complete pathological response and review of the literature]. / Place de la radiothérapie en conditions stéréotaxiques en traitement d'attente du carcinome hépatocellulaire avant transplantation hépatique : à propos d'un cas de réponse histologique complète sur explant et revue de la littérature.

Patients with hepatocellular carcinoma who are on liver transplant waiting list usually require local treatment to limit any risk of tumour growth. Historically percutaneous radiofrequency ablation or transarterial chemoembolization represented the major therapeutic alternatives. Depending on the size, or the topography of the lesion these two techniques may not be feasible. Radiation therapy under stereotactic conditions has recently emerged in the management of localized hepatocellular carcinoma as an alternative to the focused therapies performed to date. We herein report the case of a 43-year-old patient harbouring a complete histological response on explant after liver stereotactic irradiation and discuss its role in the management of hepatocellular carcinoma before liver transplantation.

[Radiation therapy planning for Hodgkin lymphoma: Focus on intensity-modulated radiotherapy, gating, protons. Which techniques to best deliver radiation?] / Technique de radiothérapie du lymphome de Hodgkin : points sur la radiothérapie conformationnelle avec modulation d'intensité, le gating, la protonthérapie. Y a-t-il des techniques à favoriser ?

The optimization of radiotherapy in these young and long-lived survivors raises the question about the interest of using modern techniques to allow a better distribution of the dose. The choice of the irradiation technique must take into account the incidence of side effects related to radiation. In this context, the definition of the target volumes as well as the verification and monitoring of the delivered processing are essential. International recommendations for treatment fields are based on the "involved node radiotherapy" concept. The best irradiation technique to use remains to be defined. The use of intensity-modulated radiotherapy improves the coverage and reduces the dose to the organs at risk with a variable gain depending on the topography of the lymph nodes: upper or lower mediastinum, right or left lateralization, the techniques used. The deep inspiration breath-hold technique allows an increase of the pulmonary volume, extension of the mediastinum with an up down of the heart which make possible to move the planning target volume away from the cardiac structures. The volumetric-modulated arctherapy technique with several arches can be particularly interesting to reduce the dose to the breasts, as well as tomotherapy when bulky disease. Proton therapy with the Bragg peak specificity can play a key role in limiting doses to organs at risk, when robust planning that will take into account geometric and physical uncertainties is available. The heterogeneity of Hodgkin lymphomas in terms of volume, shape and initial location are the key elements to take into account when choosing the preferred radiotherapy technique.

Total body irradiation using Helical Tomotherapy®: Treatment technique, dosimetric results and initial clinical experience.

PURPOSE: Helical TomoTherapy® allows precise and homogeneous tumour coverage and excellent sparing of organs at risk. We present here our treatment technique, dosimetric results, and our first clinical data for patients receiving total body irradiation as part of the conditioning regimen before hematopoietic stem cell transplantation. PATIENTS AND METHODS: The cohort consisted of 11 patients who were treated in our institution between August 2014 and January 2016. The total dose was 12Gy in six fractions in three days. We collected the dose distribution information in the treatment volumes, organs at risk and area of junction. We report retrospectively the clinical events during the first 6 months after the procedure. RESULTS: Median age was 31 years (range, 18-57 years). Median D98% was 11.5Gy (range: 6.6-11.9Gy). The median of the mean doses to the lungs was 8.7Gy (range: 8.5-9.3Gy). The mean dose for the junction area was 12Gy (range: 11.9-12.1Gy). All patients had the total procedure, and all underwent successful engraftment. During the first six months, nine patients had at least one grade 3 or 4 toxicity that was due essentially to graft versus host disease. No patient had radiation pneumonitis. The toxicities were both more frequent and of higher grade during the first three months. CONCLUSION: Total body irradiation using helical TomoTherapy® is feasible. It allows a very good homogeneity of dose and conformity with an acceptable tolerance. It could deliver higher doses to sites at high risk of recurrence (bone marrow, sanctuary sites), while sparing major normal organs like lungs, liver, and kidneys. This reduction of dose could lead to reduced severity and frequency of late complications.

[Uncommon dermatologic disorders triggered by radiation therapy of breast cancer: A case-series]. / Dermatoses réactionnelles rares après radiothérapie : une série de cas avec cancer du sein.

Radiotherapy's main skin toxicities are now well-separated, acute (acute radiation dermatitis) or chronic complications (chronic radiation dermatitis, induced cutaneous carcinoma, aesthetic sequelae). Exceptionally, radiotherapy may induce, by isomorphic reaction or Koebner's phenomenon, some specific dermatosis. In this article, we report five new observations of these unusual complications of radiation therapy, occurring in very variable time after breast irradiation and remaining strictly localized in the irradiated field (cutaneous mastocytosis, Sweet syndrome, lichen planus, vitiligo). These cases emphasize the need to realize a systematic histological exam if any atypical skin lesion appears after radiotherapy, even long after.

[Acute toxicity of breast cancer irradiation with modulated intensity by tomotherapy®]. / Toxicité aiguë de la tomothérapie des cancers mammaires.

PURPOSE: Helical radiation intensity modulated by tomotherapy improves dose distribution to complex and large volumes. The aim of the study was to assess acute toxicity of this technique during breast cancer irradiation after conserving surgery or mastectomy. PATIENTS AND METHODS: Cutaneous toxicities, lung and oesophageal side effects, and breast lymphedema were retrospectively collected according to the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) in 292 patients treated for a breast cancer by tomotherapy between May 2010 and December 2014. After conservative surgery, the dose administered to breast volume and the tumour bed was respectively 52.2Gy and 63.8Gy in 29 fractions. After mastectomy, the dose was 50Gy in 25 fractions. Univariate and multivariate analyses were performed to highlight risk factors for dermatitis and breast oedema. RESULTS: The rate of dermatitis grade 2 and 3 were 22.9% and 1.7% respectively. In univariate analysis, factors associated with acute radiation dermatitis were breast volume (P=0.002), body mass index (BMI) (P<0.0001), the use of chest compression mask (net) (P=0.005) and the localization of the irradiation (P <0.0001). In multivariate analysis, BMI greater than 25kg/m2 (odds ratio [OR]: 3.61, 95% confidence interval [CI]: [1.93-6.74], P<0.0001), the use of a chest mask (OR 2.01, 95% CI [1.06-3.79] P=0.0328) and irradiation after conservative treatment increase the risk of acute radiation dermatitis (mastectomy: OR 0.64, 95% CI [0.04-0.43]; mastectomy with immediate reconstruction with prosthesis: OR 0.13 95% CI [0.10-0.38] P=0.0003). The incidence of breast oedema grade 2 or above was 19.5%, in univariate analysis, there was a correlation with BMI (P=0.003) and smoking (P=0.009). In multivariate analysis, smoking and BMI greater than 25kg/m2 increased the risk of breast oedema (OR 2.47, respectively [95% CI 1.22-5.01] P=0.012 and OR 2.37 [95% CI 1.22-4.59] P=0.01). The rate of radiation pneumonitis of grade 2 or above was 1.4%. Among the patients, 19.9% had esophagitis grade 1 or 2. CONCLUSION: The helical irradiation intensity modulation tomotherapy is a well-tolerated treatment for breast cancer that reduces the high radiation doses to organs at risk.

[Breast ductal carcinoma in situ with microinvasion: pathological review and clinical implications]. / Carcinome canalaire in situ avec micro-invasion : spécificités anatomopathologiques et implications cliniques.

PURPOSE: Recent improvements in the detection of breast cancer at an early stage have resulted in a rising incidence of breast ductal carcinoma in situ with microinvasion. So far, there is no consensus regarding its optimal management. We hereby report on our 10-year single institutional experience in breast ductal carcinoma in situ with microinvasion including pathological reviewing. PATIENTS AND METHODS: All consecutive patients treated for a ductal carcinoma in situ with microinvasion at the Institut Claudius-Regaud (Toulouse, France) over a 10-year period were included in this study. We reviewed all available histological materials. RESULTS: Sixty-three patients were eligible for this study. Two patients presented with a lymph node invasion at diagnosis. Each patient benefited from initial surgical management, which consisted either in mastectomy (n=25) or conservative resection (n=37). Axillary exploration was performed in 52 patients (82%). After a median follow-up of 61.3 months [46.9;69], the 5-year overall survival and disease free survival were 98.2 (95% CI=[88.2;99.7]) and 89.5% (95% CI=[76.3;95.6]) respectively. Two delayed invasive relapses occurred leading to one specific death. The pathological review highlighted a trend towards a loss of HR and HER2 expression (9%) in the microinvasive component in comparison with its surrounded in situ carcinoma. CONCLUSION: The risk of initial lymph node involvement and delayed invasive local relapse deserve an optimal locoregional management including lymph node evaluation. The non-negligible discrepancy's rate between in situ and microinvasive components justifies HR status and HER2 expression assessment on the microinvasive component.

[National breast cancer brachytherapy survey in France: Results and perspectives in 2009]. / Enquête nationale sur la curiethérapie dans le cancer du sein : état des lieux et perspectives en 2009.

PURPOSE: To present the national survey patterns in France for breast cancer brachytherapy in 2009. MATERIAL AND METHOD: A written questionnaire was sent to the academic and general hospitals and the anticancer centres. The different items were type of institution; breast cancer clinical trial participation; number of breast brachytherapy per year; its indications; material and dose rate used. RESULTS: Among the 76 sent questionnaires, 35 (46 %) answers were available: 9 % of academic hospitals and 50 % of cancer centres performed breast brachytherapy. The number of breast brachytherapy per year ranged between 300 and 350. The indications were boost (100 %), partial breast irradiation (20 %) and second conservative treatment for local recurrence (53 %). The implanted material consisted in needles (27 %) and plastic tubes (73 %). The dose rate was low (50 %), pulsed (25 %) and high (25 %). CONCLUSION: Breast brachytherapy appears as a validated technique in case of boost but remains under investigation for partial breast irradiation and second conservative treatments. Good clinical practice rules as well as technical and dosimetric guidelines are needed. A cost-effective analysis of breast brachytherapy is warranted.

Pre-operative radiotherapy as adjuvant treatment in rectal cancer.

From January, 1975 to December, 1987, 241 patients with rectal cancer underwent pre-operative irradiation and surgical resection. The radiation was delivered with 25 MeV photons, 5 days per week by 2.4 grays fractions up to a total dose of 36 grays. Surgery was curative in 195 patients; 57% had abdomino-perineal resection. Irradiation had to be discontinued in 3 patients and 4 patients subsequently developed severe acute ileitis. Postoperative mortality rate was 2.9%. The most frequent postoperative complications were delayed healing of abdominal wounds (18%) and perineal wounds (14%). Severe late complications occurred in 27 (13%) patients. The incidence of intestinal obstruction was 5%. Follow-up survivors ranged from 18 months to 13 years. Local failure occurred in 24 (12%) of the 195 patients. Local failure rates were 10% for Dukes' A tumors, 11.6% for Dukes' B, and 22.7% for Dukes' C tumors. Five and 10 year actuarial survival rates after curative surgery were 70% and 52%. The Dukes' classification was the only factor that influenced survival.

Non-randomized comparative study of irradiation alone or in combination with surgery in stage Ib, IIa and "proximal" IIb carcinoma of the cervix.

252 evaluable patients were treated in the Centre Claudius Regaud from January 1974 to December 1983 for stage Ib, IIa or proximal IIb carcinoma of the uterine cervix. This retrospective analysis compares results obtained either by radio-surgical combination therapy (113 patients = RS group) or by exclusive irradiation (139 patients = RT group). The comparison of the two groups in terms of patient age, obesity, associated vascular pathology and previous abdomino-pelvic surgery favored the RS group significantly. The distribution according to clinical stage also significantly favored the RS group. The proportion of patients with stage IIb disease was 12% in the RS group as opposed to 25% for the RT group. Despite unfavorable patient and tumor characteristics, therapeutic results in the RT group were similar to those of the RS group. Pelvic recurrences developed in 18/110 (16%) and 18/139 (13%) of the patients in the RS and RT groups, respectively. Distant metastases occurred in 5/92 (5%) patients in the RS group and 13/121 (11%) patients in the RT group, but the difference was not significant (p less than 0.1). Five year corrected actuarial disease-free survival was 82% in both groups. There were no major early complications in the RT group while four were found in the RS group, of which three were fatal. 2% of patients had major late complications in the RS group versus 6% in the RT group and none were lethal. 25% of the RT group patients had a moderate or mild complication versus 10% in the RS group but 2/3 of these complications recovered without sequellae.

[Role and results of radiotherapy in the treatment of pancreatic adenocarcinoma]. / Place et résultats de la radiothérapie dans le traitement des adénocarcinomes pancréatiques.

Most pancreatic carcinomas are clinically observed when the tumoral spread is well advanced. Consequently, surgical excision is very often either partial or unfeasible. However, evolutive patterns of pancreatic carcinomas show a long past history of loco-regional spread before the onset of visceral metastasis. Consequently, radiotherapy could be proposed to treat locally advanced pancreatic tumors or residual disease after surgical excision in curative intend. The major challenge dealing with radiotherapeutic management of pancreatic carcinomas is to safely deliver doses as high as 60-70 Gy into the upper half of the abdominal cavity. Several technical conditions must be fulfilled before this can take place: high energy and multiple convergent photon beams, precise surgical and/or radiological description of tumoral extent, careful sparing of critical tissues such as spinal cord and kidneys. Usually, radiotherapeutic planning is administered in 2 successive sessions: 40-45 Gy are first administered to the tumor and main nodal drainage over 4-6 weeks, then a 15-25 Gy boost dose is given to the primary tumor bed only. However, postoperative irradiation after complete removal of a gross tumor gives a 10% survival rate only at 2 years. Improvement of these results, are eventually expected from intra-operative irradiation techniques or radiochemotherapy combined treatments.

The incidence of severe chronic ileitis after abdominal and/or pelvic external irradiation with high energy photon beams.

The authors report a 7.9% incidence of late severe ileal complications after abdominal and/or pelvic external radiation therapy in 188 consecutive patients. All treatments were performed using 25 MV photon beams, with AP-PA field technique, a daily dose of 1.8-2 Gy, 5 times a week. One hundred and two (54.3%) patients were given whole pelvic irradiation up to 45-55 Gy without a boost, 64 patients (34%) received boost doses on limited volumes up to 60-65 Gy. The analysis of factors which could be useful in predicting a high risk of severe ileal sequellae, has shown that the main factor was the past history of previous laparotomy. Thus, the incidence of chronic ileitis in patients who have never been laparotomized in the past and who were treated by radiotherapy alone, was 2.2% (2/97); in contrast patients with previous abdominal surgery whatever its purpose, showed in 13/91 cases (14.3%) severe ileal complications (p less than 0.05). In addition, the risk of chronic ileitis increases with the number of previous laparotomies irrespective of delay or purpose: 10.1% after one laparotomy, 22.2% after two and 50% after three or more laparotomies. The influence of these data on the planning of abdominal and/or pelvic external irradiation is discussed.