D. Peurien

Helical Tomotherapy for Inoperable Breast Cancer: A New Promising Tool

Background. We investigated the feasibility of helical tomotherapy (HT) for inoperable large breast tumors, after failing to achieve adequate treatment planning with conformal radiation techniques. Material and Methods. Five consecutive patients with locally advanced breast cancer (LABC) were treated by preoperative HT. All patients received up-front chemotherapy before HT. Irradiated volumes included breast and nodal areas (45–50 Gy) in 4 patients. One patient received a simultaneous integrated boost (55 Gy) to gross tumor volume (GTV) without lymph node irradiation. Acute toxicity was assessed with Common Toxicity Criteria for Adverse Events v.4. Patients were evaluated for surgery at the end of treatment. Results. Patients were staged IIB to IIIC (according to the AJCC staging system 2010). HT was associated in 4 patients with concomitant chemotherapy (5-fluorouracil and vinorelbine). Two patients were scored with grade 3 skin toxicity (had not completed HT) and one with grade 3 febrile neutropenia. One patient stopped HT with grade 2 skin toxicity. All patients were able to undergo mastectomy at a median interval of 43 days (31–52) from HT. Pathological partial response was seen in all patients. Conclusions. HT is feasible with acceptable toxicity profiles, potentially increased by chemotherapy. These preliminary results prompt us to consider a phase II study.

Résultats préliminaires d’une tomothérapie hélicoïdale adjuvante avec boost intégré dans le cadre d’un traitement conservateur d’un cancer du sein

PURPOSE To evaluate the dosimetry and acute toxicity of helical tomotherapy for locoregional irradiation of patients after breast-conserving surgery. PATIENTS AND METHODS Twenty breast cancer patients with breast-conserving surgery treated by helical tomotherapy have been studied. The median age was 49 (min: 25, max: 69). The whole breast, tumour bed and lymph nodes were prescribed 52.2 Gy, 63.8 Gy and 50.4 Gy, all in 29 fractions. The dose per fraction was 2.2 Gy to the boost, 1.8 Gy to the breast and 1.74 Gy to the lymph node volumes. The reproducibility was analysed by recording the daily shifts in x, y and z directions and roll rotation. All toxicities were described using the Common Terminology Criteria for Adverse Effects v3.0. RESULTS Twenty-two tumours were irradiated. Six-eight percent were located in the inner quadrant. In 90 % of patients supraclavicular and internal mammary nodes were treated. The coverage of planning target volumes (PTV) was as follows: PTV boost: V107 = 0.3 % ± 0.5 SD, V95 = 98.4 % ± 1.9 SD; PTV breast: -V107 = 7.8 % ± 17.3 SD, V95 = 96.8 % ± 2.2 SD; PTV LN: V107 = 2.5 % ± 4.2 SD, V95 = 92.7 % ± 13.2 SD. The mean V20 of the homolateral lung was 18.9 % ± 3.5 SD. For left side lesion, the mean V30 of the heart was 0.9 % ± 0.8 SD. The mean V5 was: V5 homolateral lung: 73.1 % ± 11.8 ET, controlateral lung: 38.9 % ± 21, heart (left side breast): 57.3 % ± 21, controlateral breast: 15.5 % ± 9.6. Median shifts were as follow: x-axis -0.04 mm (IC 95: -0.4 +0.38), y-axis -0.37 mm ± 5.51 (IC 95: -0.88 +0.14), z-axis 2.90 mm ± 5.42 (IC 95:+2.4+3.4) and roll rotation 0.22 ± 1.10 (IC 95: -0.1+0.32). The treatment tolerance was acceptable with 1 definitive interruption couple of fractions before the end and 3 temporal interruptions for skin toxicity. No grade 3 or 4 toxicity. Ninety-five percent of patients experienced skin toxicity: 45 % grade 2. There were 3 cases of oesophagitis. The median follow-up of presented series is 9.7 months and all of the patients are free of disease without any residual early or late toxicity. CONCLUSIONS Helical tomotherapy can achieve full target coverage while protected to the heart and ipsilateral lung. This treatment was well tolerated and reproducible. However, the low doses to normal tissue volumes need to be reduced in future studies.

Use of deformable image fusion to allow better definition of tumor bed boost volume after oncoplastic breast surgery

Although the use of boost irradiation is recommended, the standard technique and definition of the boost volume after oncoplastic surgery have not been clearly established. This multidisciplinary study based on image registration was designed to propose practical solutions for the definition of tumor bed boost in this setting.

Plastic surgery for breast conservation therapy: How to define the volume of the tumor bed for the boost?

PURPOSE To describe the procedure of definition of the boost volume using pre- and post-operative computed tomography (CT) and surgical clips in the tumor bed after oncoplastic surgical procedure. PATIENTS AND METHODS Thirty-one consecutive breast cancer patients who underwent simple lumpectomy or oncoplastic surgery were studied. All of them underwent pre- and post-operative CT scan in treatment position to evaluate the planning target volume (PTV) boost volume and define the primary tumor (gross tumor volume (GTV)) and tumor bed zones (CTV), with an overall margin of 5 mm in lateral and 10 mm in craniocaudal directions, corresponding to localization and setup uncertainties. RESULTS Thirteem patients underwent simple lumpectomy and 18 oncoplastic surgery. The volumetric analysis showed that the intersection between GTV and CTV clips was significantly higher in patients with three and more clips (28.4% vs 3.14%; p < 0.001). In the case of patients with oncoplastic surgery, more than three clips were needed to define the tumor bed volume with accuracy. The number of clips was directly related to the exact definition of the boost volume. CONCLUSIONS The use of more than three clips allows better definition of the PTV boost volume after oncoplastic surgical procedure.

Comparison of passive-beam proton therapy, helical tomotherapy and 3D conformal radiation therapy in Hodgkin's lymphoma female patients receiving involved-field or involved site radiation therapy

PURPOSE Second cancers and cardiovascular toxicities are long term radiation toxicity in locally advanced Hodgkins lymphomas. In this study, we evaluate the potential reduction of dose to normal tissue with helical tomotherapy and proton therapy for Hodgkins lymphoma involved-field or involved-site irradiation compared to standard 3D conformal radiation therapy. PATIENTS AND METHODS Fourteen female patients with supradiaphragmatic Hodgkins lymphoma were treated at our institution with 3D conformal radiation therapy or helical tomotherapy to a dose of 30Gy in 15 fractions. A planning comparison was achieved including proton therapy with anterior/posterior passive scattered beams weighted 20Gy/10Gy. RESULTS Mean doses to breasts, lung tissue and heart with proton therapy were significantly lower compared to helical tomotherapy and to 3D conformal radiation therapy. Helical tomotherapy assured the best protection of lungs from doses above 15Gy with the V20Gy equal to 16.4%, compared to 19.7% for proton therapy (P=0.01) or 22.4% with 3D conformal radiation therapy (P<0.01). Volumes of lung receiving doses below 15Gy were significantly larger for helical tomotherapy than for proton therapy or 3D conformal radiation therapy, with respective lung doses V10Gy=37.2%, 24.6% and 27.4%. Also, in the domain of low doses, the volumes of breast that received more than 10Gy or more than 4Gy with helical tomotherapy were double the corresponding volumes for proton therapy, with V4Gy representing more than a third of one breast volume with helical tomotherapy. CONCLUSIONS Helical tomotherapy achieved a better protection to the lungs for doses above 15Gy than passive proton therapy or 3D conformal radiation therapy. However, dose distributions could generally be improved by using protons even with our current passive-beam technology, especially allowing less low dose spreading and better breast tissue sparing, which is an important factor to consider when treating Hodgkins lymphomas in female patients. Prospective clinical study is needed to evaluate the tolerance and confirm these findings.

Can we Reduce the Toxicity of the Mediastinal Irradiation Using NewHighly Conformal Techniques

Objectives: Three-Dimensional Conformal Radiotherapy (3DCRT) has been successfully used to treat Hodgkin’s Lymphoma (HL) but treatment delivery is often complex and requires large fields that may result in significant exposure of normal tissues to ionizing radiation. The present study was undertaken to compare the dosimetry of Involved Field (IF) 3DCRT to HT in female patients treated for HL. Materials/Methods: A total of 10 young female patients affected with early stage mediastinal HL and treated with IF radiotherapy after chemotherapy were selected from our database. For each patient, 3DCRT and HT plans were designed to deliver 30 Gy to the target volume and 36 Gy in case of residual masses. HT planning solutions were optimized by inverse planning with specific dose-volume constraints on OAR (breasts, lungs, heart). Dose- Volume Histograms (DVHs) were calculated and then compared, both for target and OAR by a statistical analysis (Wilcoxon’s Test). Results: Mean doses to the PTV were almost identical for all plans. Conformity index was better with HT and homogeneity index didn’t differ. Mean dose to the breasts were increased with HT compared to 33DCRT (right breast: 3.28 vs 2.19, p<0.05; left breast: 3.76 vs 2.81, p<0.05) whereas no difference in mean doses appeared for heart, coronary arteries, lungs, thyroid and normal tissue. Maximal doses were reduced with HT for breasts (right breast: 19.9 vs 28.87, p<0.05; left breast: 24.76 vs 30.29, p<0.05) and spinal cord (20.87 vs 33.88, p<0.05). Volume exposed to high doses was smaller with HT whereas volume exposed to low doses was smaller with 3DCRT. Pronounced benefits of HT in terms of heart sparing were observed for patients with lymph nodes anterior to the heart. Conclusions: Although high dose to organ at risk was reduced with HT, increasing low dose especially to the breasts must be taken into account for IF HT. HT may be considered for large PTV especially when the anterior mediastinum is involved.

The use of helical tomotherapy in the treatment of early stage breast cancer: indications, tolerance, efficacy—a single center experience

Purpose to evaluate our experience in terms of local control, survival, adverse effects in patients treated by adjuvant helical tomotherapy (HT) for breast cancer (BC). Results We studied 179 consecutive patients with 194 treated breasts with adjuvant HT. Median follow-up was 38.1 months. Median age was 53 years. Chemotherapy was administered to 83% of patients. All 133 hormone receptor positive tumours received hormonal therapy. As concurrent treatment, apart from trastuzumab monotherapy, 6 patients received systemic therapy concomitant to RT. The HT was generally well tolerated with mostly grade 1 and 2 skin reactions and esophagitis. Only 3% grade III early skin reactions. At last follow-up, there were 2 local recurrences, 1 regional lymph node (LN) recurrence and 6 with metastatic progression. The 5-year progression-free survival was 90.5% (95% CI 84.2–97.3). Materials and Methods A retrospective study of all patients treated by HT between 2009 and 2015 was done. Patients excluded were those with: breast implants, advanced or metastatic BC, recurrent disease. All patients received breast+/-boost or chest wall irradiation and most received with LN irradiation. Dose constraints for organs at risk were defined using optimization scale developed in our Department. Evaluation of early and late toxicity was done using Common Terminology Adverse Criteria Events v.4.0. Conclusions HT can be used for a well selected group of breast cancer as bilateral tumours, complex anatomy and target volumes where the conventional radiation therapy techniques cannot ensure an optimal dose distribution. Longer follow-up is necessary to confirm and validate these results.

Use of helical tomotherapy in locally advanced and/or metastatic breast cancer for locoregional treatment

OBJECTIVE Helical tomotherapy (HT) is a new promising tool whose use remains to be studied. This work assesses its impact for local irradiation in terms of side effects, as well as tumour control in locally advanced (LABC) and metastatic breast cancer (MBC). METHODS We retrospectively reviewed data of 66 patients with LABC and MBC. Patients received standard fractionated radiotherapy by HT, with or without concurrent systemic treatment. RESULTS The median age was 60 years (28-77). The median follow-up of the population was 35.9 months (10.6-95.8). For 91% of patients, HT was concomitant with systemic treatments. Three patients experienced grade 3 skin toxicity and all had concurrent 5FU-vinorelbine. One patient who was receiving concurrent treatment with trastuzumab-pertuzumab had a decreased left ventricular ejection fraction by 14%. No late cardiac or lung toxicity was observed. A clinical benefit was observed in 75% of cases. At 2 months after HT, we observed tumour regression in 7/8 patients, as following: 1 complete, 4 partial responses, and 2 stable disease. The median survival for MBC group was 64.4 months (42.6-65.8) and 21.1 (6.1-36.1) months for LABC. CONCLUSION This study suggests that the use of HT is well tolerated and feasible with a multimodal strategy that includes concurrent systemic treatments for patients with LABC and MBC. Advances in knowledge: The survival of LABC and MBC increases and new safe tools are needed to determine optimal strategies of treatment. To our knowledge, this is the first paper describing the use of HT for this population.

Can Helical Tomotherapy be used as a Safe Treatment Alternative for Breast Cancer Patients

Radiation therapy (RT) has demonstrated strong clinical benefits for patients who present a high relapse risk after breast conserving surgery or radical mastectomy. Unfortunately, the benefits of RT can be offset by its possible impacts on cardiac toxicity and increased risk of death from cardiac events. Additionally, recent radiological and radiotherapy techniques have allowed clinicians to better define target volumes and customize irradiation so that doses to the heart and left coronary artery can be accurately quantified. Alternative treatment positions, such as the lateral and prone positions are also being used. These positions can adapt to the patient’s anatomy and thus better protect the heart and lungs. This paper will report the outcomes for a patient who received breast cancer treatment after her treatment position and technique were optimized for ideal target volume coverage and minimum irradiation to organs at risk (OAR), particularly to the heart and lungs.