Long-term efficacy and tolerance of a technique for postmastectomy electron beam radiation therapy of the unreconstructed chest wall and lymph node areas for non-metastatic breast cancers.

PURPOSE: To evaluate the long-term tolerance and outcome of patients irradiated with an electron beam technique used since 2007 on the chest wall and lymph node areas after mastectomy for non-metastatic locally advanced breast carcinoma. PATIENTS AND METHODS: All patients irradiated with an improved electron beam technique after mastectomy for non-metastatic breast carcinoma between 2007 and 2011 at Institut Curie (France) were included in this descriptive study. The technique has already been described in other studies, as has its 5-year tolerance and non-inferiority compared to photon irradiation. Acute and chronic toxicity were collected using CTCAE v 3.0. A clinical examination was carried out each week during the radiotherapy and at each 6 months consultation with one mammogram per year at the Institut Curie for at least 5 years. The patients then continued to be followed either at the Institut Curie or in private practice with a good transmission of outpatient consultations, thanks to a system of forms to be completed and integrated into the electronic files. Quantitative and qualitative data are defined by mean and proportion. Statistical comparisons were made by computer using the Chi2 test and Fisher's exact test for categorical variables. Recurrence-free survival was defined as the time between the end of treatment and the date of recurrence or death. Overall survival was defined in the same way without taking into account recurrences. Patients who did not report any events were censored at the date of last news. RESULTS: Of the 796 patients included, 51.3% had multifocal lesions, 10.1% had triple negative status, and 18.8% displayed overexpression of the Her2 receptor, 196 (24.6%) patients received neoadjuvant chemotherapy and 208 (26.1%) systemic treatment during radiotherapy (chemotherapy or targeted therapy); 514 (64.6%) had at least one positive lymph node. The internal mammary chain (IMC) was irradiated in 85.6% of cases, the supraclavicular areas in 88.3% of cases, the infraclavicular in 77.9% of cases and the axillary area in 14.9% of cases. With a median follow-up of 113 months (range: 2-164 months), locoregional recurrence-free survival and overall 10-year survival was respectively 94.02%, (95% CI: 92.13-98.94) and 79.84% (95% CI: 76.83-82.97). Median survival was not reached. In the long term, 29.6% of patients had telangiectasias (grade 1: 23.3%, grade 2: 5.2%, grade 3: 1.1%). There were 279 patients (35.1%) with secondary breast reconstruction on average 21 months after all treatments. IMC irradiation was not associated with a majority of pulmonary toxicity. Thirty-five patients developed chronic heart disease after radiotherapy, 30 of whom had received anthracyclines and 9 had received traztuzumab. Three of these reported a coronary ischaemic event, including 2 irradiated on the left and 1 on the right, the 4 were irradiated in the vicinity of the IMC and the other lymph node areas, but presented many other cardiovascular risk factors (between 2 and 4). During follow-up, 4.9% of patients had a contralateral recurrence (n=39) and 5.5% had a second non-breast cancer (n=44), of the 6 bronchopulmonary cancers diagnosed, none appeared to be related to chest wall radiotherapy. CONCLUSION: This study confirms that the improved postmastectomy electron beam radiation therapy technique is well-tolerated after nearly 10 years of follow-up.

Radiation dose to the low axilla in patients treated for early-stage breast cancer by locoregional intensity-modulated radiotherapy (IMRT).

PURPOSE: To determine the dose received by the low axilla during locoregional radiotherapy (RT) for early-stage breast cancer and to assess the impact of the treatment technique (three-dimensional conformal radiotherapy (3D-CRT) or rotational IMRT (VMAT) or helical tomotherapy (HT). MATERIALS AND METHODS: The dosimetric study was performed on patients receiving normofractionated (NFRT - 50Gy in 25 fractions) or hypofractionated (HFRT - 40Gy in 15 fractions) locoregional radiotherapy (breast or chest wall and internal mammary, supraclavicular and infraclavicular nodes±axillary nodes) by 3D-CRT or VMAT or HT at the Institut Curie Paris. Patients treated by breast-conserving surgery received a boost dose of 16Gy and 10Gy to the tumour bed, respectively. RESULTS: Sixty-eight patients treated by RT from February 2017 to January 2019 were studied. The mean dose received by the low axilla when it was not part of the target volume was 30.8Gy, 41.0Gy and 44.4Gy by 3D-CRT, VMAT and HT, respectively for NFRT and 24.2Gy, 33.0Gy and 34.9Gy, respectively, for HFRT. With NFRT, 4.1% of the axilla received 95% (V95) of the prescribed dose by 3D-CRT compared to 24.5% and 33.6% by VMAT and HT, respectively; with HFRT, V95 was 3.9%, 19.5% and 24.1%, respectively. CONCLUSION: The axilla receives a non-negligible dose during locoregional radiotherapy; this dose is greater when VMAT or HT are used. Prospective studies must be conducted to assess the impact of this axillary dose in terms of morbidity, which currently remains unknown.

Dosimetric comparison of four high performance techniques for irradiation of breast cancer patients.

PURPOSE: The use of IMRT for the treatment of breast cancer has been growing considerably in our institution since 2009. Alternatively, helical tomotherapy (HT) using a field width of 2.5 and 5cm (HT_FW_5), volumetric-modulated arc therapy (VMAT), or proton therapy with pencil-beam scanning (PT-PBS) have also been used to reduce treatment duration or optimize organ-at-risk (OAR) sparing. The purpose of this study was to compare the 4 treatment modalities available at our site. PATIENTS AND METHODS: We studied 10 patients treated for breast cancer with lymph node involvement. The prescribed dose was 51.8Gy to the breast with a simultaneous integrated boost up to 63Gy, and 50.4Gy to lymph nodes in 28 fractions. The CTV was delineated according to ESTRO Guidelines. Dosimetric planning in routine clinical practice was performed using HT_FW_2.5. The approved clinical plan was compared to the 3 other plans. Dosimetric goals for PTV coverage were D95%≥95% and D2%≤107% of the prescribed dose. Mean and maximum doses to OAR were recorded. RESULTS: HT_FW_5 and VMAT plans ensure equivalent or even better PTV coverage compared to the initial clinically approved plan but at the cost of poorer OAR sparing. PT_PBS plans showed that an excellent PTV coverage can be maintained with significantly lower doses to OAR. CONCLUSION: HT_FW_5 and VMAT plans allow a significant reduction of treatment duration and can be a good alternative to HT_FW_2.5 for specific populations. HT_FW_2.5 could be chosen for patients at higher risk of side effects. In addition, PT_PBS should be considered in the near future as it has been shown to have a major potential benefit to lower the risk of side effects with the same level of PTV coverage.

Protontherapy of head and neck paragangliomas: A monocentric study.

PURPOSE: The aim of this study was to assess efficacy and safety of proton beam therapy of paragangliomas of the head and neck, rare benign tumours developed close to crucial structures such as cranial nerves and vascular tissues. PATIENTS AND METHODS: Ten patients with a paraganglioma of the head and neck were treated from 2001 to 2014 with image-guided proton therapy. Neurological and ear nose throat symptoms were collected in addition to audiometric testing, before and after the treatment. Acute and late toxicities were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4. RESULTS: Median age at diagnosis was 52.6years (range: 18.2-65.8years). Proton therapy was the exclusive treatment in six patients and four patients had a postoperative radiotherapy. Median dose was 50.4Gy relative biological effectiveness (RBE; range: 45.0-67.0Gy). With a median follow-up of 24.6months (range: 6.7-46.2 months), local tumour control rate was 100% (stable, n=10). No upper grade 2 acute toxicity was reported. To the latest news, seven patients had controlled symptoms (improved, n=1, stabilized, n=6). One patient out of seven with initial tinnitus had a decrease in his symptoms, while the six other patients had a sustained stabilization. CONCLUSION: Proton beam therapy is an effective and well-tolerated treatment modality of skull base paragangliomas, with documented functional benefit. A longer follow-up is planned in order to assess local control and long-term toxicities.

[Helical tomotherapy in the treatment of malignant pleural mesothelioma: The impact of low doses on pulmonary and oesophageal toxicity]. / Tomothérapie hélicoïdale dans le traitement du mésothéliome pleural malin : impact des faibles doses sur la toxicité pulmonaire et œsophagienne.

PURPOSE: To evaluate the adjuvant treatment of malignant pleural mesothelioma by helical tomotherapy and the impact of low doses on esophageal and pulmonary toxicity. PATIENTS AND METHODS: Between June 2007 and May 2011, 29 patients diagnosed with malignant pleural mesothelioma received adjuvant radiotherapy by helical tomotherapy. The median age was 63 years (34-72). Histologically, 83 % of patients had epithelioid malignant pleural mesothelioma. Clinically, 45 % of patients were T3 and 55 % N0. Eighty six percent of the patients were treated by extrapleural pneumonectomy and 35 % received neoadjuvant chemotherapy with platinum and pemetrexed. The median dose in the pneumonectomy cavity was 50Gy at 2Gy/fraction. RESULTS: The mean follow-up was 2.3 years after diagnosis. Overall survival at 1 and 2 years was 65 and 36 % respectively. The median survival from diagnosis was 18 months. Median lung volumes receiving 2, 5, 10, 13, 15 and 20Gy (V2, V5, V10, V13, V15 and V20) were 100, 98, 52, 36, 19 and 5 %. The median of the mean remaining lung dose was 11Gy. Two patients died of pulmonary complications, three patients had grade 3 lung toxicity, while esophageal grade 3-4 toxicity was observed in three other patients. No significant impact of clinical characteristics and dosimetric parameters were found on pulmonary toxicity, however a V10≥50 %, a V15≥15 % and mean lung dose of 10Gy or more had a tendency to be predictive of pulmonary toxicity (P<0.1). Moreover, in our analysis, the mean lung dose seems to have a significant impact on esophageal toxicity (P=0.03) as well as low doses to the controlateral lung: V5, V10 and V13 (P<0.05). CONCLUSION: Helical tomotherapy is a promising technique in the multimodality treatment of malignant pleural mesothelioma. Low doses received by the contralateral lung appear to be the limiting factor. A dosimetric comparison with volumetric modulated arctherapy techniques would be interesting in this setting.

[Localized Ewing sarcoma of the spine: a preliminary dose-escalation study comparing innovative radiation techniques in a single patient]. / Sarcomes d'Ewing localisés du rachis chez l'enfant : étude préliminaire d'escalade de dose comparant les techniques innovantes.

PURPOSE: Although radiosensitive, spinal locations of Ewing's sarcomas are challenging for the radiation oncologist due to poor radiation tolerance of the spinal cord. However, some favorable anatomical compartments - that may represent more than 20% - were associated with a better outcome and could benefit from a radiation dose escalation using the most recent radiation therapy techniques. MATERIALS AND METHODS: We performed a dose escalation study on one patient, declined in two scenarios: (1) a tumour located within a single vertebral body and (2) a locally advanced disease involving the vertebral foramen and paraspinal soft tissues. Five dose-levels are proposed: 44.8Gy, 54.4Gy, 59.2Gy, 65.6Gy and 70.4Gy (1.6Gy per session, 8Gy per week). The 3D-conformational technique is compared with static intensity modulated radiation therapy (IMRT), helical tomotherapy, volumetric modulated arc therapy (VMAT), stereotactic body robotic radiation therapy (SBRT) and protontherapy (passive scattering). Two constraints had to be respected in order to skip to the next level: the planned target volume (PTV) coverage must exceed 95% and the D(2%) on the spinal cord shall not exceed a given constraint set at 50Gy in case 1 and 44Gy in case 2 due to initial neurological sufferance. RESULTS: Only protontherapy, SBRT, helical tomotherapy and VMAT appear able to reach the last dose level while respecting the constraints in case 1. On the other hand, only helical tomotherapy seems capable of reaching 59.2Gy on the PTV in case 2. CONCLUSION: With the most recent radiation therapy techniques, it becomes possible to deliver up to 70.4Gy in a favorable compartment in this sham patient. Unfavorable compartments can receive up to 59.2Gy. Definitive radiation therapy may be an interesting local treatment option to be validated in an early phase trial.