C. Chargari

Preliminary Results of Whole Brain Radiotherapy With Concurrent Trastuzumab for Treatment of Brain Metastases in Breast Cancer Patients

PURPOSEnTo assess the use of trastuzumab concurrently with whole brain radiotherapy (WBRT) for patients with brain metastases from human epidermal growth factor receptor-2-positive breast cancer.nnnMETHODS AND MATERIALSnBetween April 2001 and April 2007, 31 patients with brain metastases from human epidermal growth factor receptor-2-positive breast cancer were referred for WBRT with concurrent trastuzumab. At brain progression, the median age was 55 years (range, 38-73), and all patients had a performance status of 0-2. The patients received trastuzumab 2 mg/kg weekly (n = 17) or 6 mg/kg repeated every 21 days (n = 14). In 26 patients, concurrent WBRT delivered 30 Gy in 10 daily fractions. In 6 patients, other fractionations were chosen because of either poor performance status or patient convenience.nnnRESULTSnAfter WBRT, radiologic responses were observed in 23 patients (74.2%), including 6 (19.4%) with a complete radiologic response and 17 (54.8%) with a partial radiologic response. Clinical responses were observed in 27 patients (87.1%). The median survival time from the start of WBRT was 18 months (range, 2-65). The median interval to brain progression was 10.5 months (range, 2-27). No Grade 2 or greater acute toxicity was observed.nnnCONCLUSIONnThe low toxicity of trastuzumab concurrently with WBRT should probably not justify delays. Although promising, these preliminary data warrant additional validation of trastuzumab as a potential radiosensitizer for WBRT in brain metastases from breast cancer in the setting of a clinical trial.

Concurrent capecitabine and whole-brain radiotherapy for treatment of brain metastases in breast cancer patients

Preclinical data have demonstrated that ionizing radiation acts synergistically with capecitabine. This report retrospectively assessed the use of capecitabine concurrently with whole-brain radiotherapy (WBRT) in patients with brain metastases from breast cancer. From January 2003 to March 2005, five breast cancer patients with brain metastases were referred for WBRT with concurrent capecitabine. Median age was 44xa0years (range: 38–53). The median dose of capecitabine was 1,000xa0mg/m2 twice daily for 14xa0days (day1–14). Treatment cycles were repeated every 21xa0days, concurrently with WBRT (30xa0Gy, 3xa0Gy per fraction, 5xa0days per week). Median survival after starting WBRT plus capecitabine was 6.5xa0months (range 1–34xa0months). One patient achieved a complete response. Two patients achieved partial response, including one with local control lasting until most recent follow-up. One patient had stable disease. The remaining patient was not assessable for response because of early death. Most commonly reported adverse events were nausea (nxa0=xa02) and headache (nxa0=xa02), always grade 1. Other toxicities were grade 3 hand/foot syndrome (nxa0=xa01), moderate anemia requiring transfusion and dose reduction of capecitabine (nxa0=xa01), and grade 1 mucositis (nxa0=xa01). Although promising, these preliminary data warrant further assessment of capecitabine-based chemoradiation in brain metastases from breast cancer and need to be further validated in the setting of a clinical trial.

Further developments for improving response and tolerance to irradiation for advanced renal cancer: concurrent (mTOR) inhibitor RAD001 and helical tomotherapy

SummaryPurpose Radiotherapy remains marginal in the treatment of renal cell carcinoma (RCC), due to radioresistance and risks of acute toxicity. However, recent data have shown that the m-TOR inhibitors could decrease the tumor resistance to ionizing radiation. At the same time, new highly conformal irradiation modalities may significantly improve the tolerance to radiation. Methods Here, we report the first case of concurrent use of mTOR antagonist, rapamycin and Helical Tomotherapy and its potential in critical organs sparing in a patient with retroperitoneal relapse from a RCC. He was treated with Everolimus, 10xa0mg/d and concurrent Helical Tomotherapy to the region of the recurrence (45xa0Gy, 1.8xa0Gy per fraction). Results Helical Tomotherapy allowed very sharp dose distributions around the target volumes, while sparing critical organs from useless radiation. No radiotherapy related acute toxicity was observed. At last follow-up (6xa0months later), the patient remains in partial remission at the irradiated region. Conclusions While targeted agents might find applications for radiosensitizing purposes, this report highlights the potential of Helical Tomotherapy for reducing the doses delivered to the critical organs, thus improving tolerance to irradiation.

Solitary plasmocytoma: improvement in critical organs sparing by means of helical tomotherapy

Purpose:u2002 Helical tomotherapy (HT) was assessed in two patients with paramedullar solitary bone plasmocytoma. We compared doses delivered to critical organs, according HT plan or tridimensional conformal plan.

The impact of the loco-regional treatment in elderly breast cancer patients: Hypo-fractionated exclusive radiotherapy, single institution long-term results

PURPOSEnTo assess the efficacy of exclusive hypo-fractionated radiotherapy (HFRT) without previous breast-conserving surgery (BCS) in elderly women.nnnMATERIALS AND METHODSnFrom 1995 to 1999, we have treated with breast-conserving treatment 396 patients older than 70 years with early-stage breast cancer (T1,T2 tumours) at the Institut Curie, Paris, France. Seventy-nine consecutive elderly non-metastatic patients treated for early breast cancer have been treated with HFRT. Of them, 50 underwent BCS followed by HFRT of 32.5 Gy/5 fractions/5 weeks, and 29 patients (presented with different co-morbidities, inoperable or patients refusal, and/or transportation problems) received the same HFRT schedule followed by a 13 Gy boost (two fractions of 6.5 Gy) as exclusive radiotherapy treatment. This population of 29 patients has been studied. In case of hormonal positive status, hormonal therapy was also proposed to the patients.nnnRESULTSnThere was a median follow-up of 93 months (9-140 months). At 7-year follow-up, the cause-specific survival was 96.4% (confidence interval (CI) 95: 89.8.6-100%), the metastasis-free survival rate was 92.4% (CI 95: 82.8-100%) and the loco-regional control rate was 95.8% (CI 95: 88.2-100%).nnnCONCLUSIONSnThis long-term follow-up retrospective study demonstrated acceptable local control and good outcome in elderly patients treated by exclusive HFRT for early breast cancer. However, large-scale prospective randomised trials are needed to confirm these results.

Case study thoracic radiotherapy in an elderly patient with pacemaker: The issue of pacing leads

To assess clinical outcome of patients with pacemaker treated with thoracic radiation therapy for T8-T9 paravertebral chloroma. A 92-year-old male patient with chloroma presenting as paravertebral painful and compressive (T8-T9) mass was referred for radiotherapy in the Department of Radiation Oncology, Institut Curie. The patient presented with cardiac dysfunction and a permanent pacemaker that had been implanted prior. The decision of Multidisciplinary Meeting was to deliver 30 Gy in 10 fractions for reducing the symptoms and controlling the tumor growth. The patient received a total dose of 30 Gy in 10 fractions using 4-field conformal radiotherapy with 20-MV photons. The dose to pacemaker was 0.1 Gy but a part of the pacing leads was in the irradiation fields. The patient was treated the first time in the presence of his radiation oncologist and an intensive care unit doctor. Moreover, the function of his pacemaker was monitored during the entire radiotherapy course. No change in pacemaker function was observed during any of the radiotherapy fractions. The radiotherapy was very well tolerated without any side effects. The function of the pacemaker was checked before and after the radiotherapy treatment by the cardiologist and no pacemaker dysfunction was observed. Although updated guidelines are needed with acceptable dose criteria for implantable cardiac devices, it is possible to treat patients with these devices and parts encroaching on the radiation field. This case report shows we were able to safely treat our patient through a multidisciplinary approach, monitoring the patient during each step of the treatment.

FEASIBILITY OF HELICAL TOMOTHERAPY FOR DEBULKING IRRADIATION BEFORE STEM CELL TRANSPLANTATION IN MALIGNANT LYMPHOMA

PURPOSEnPreliminary clinical experience has suggested that radiation therapy (RT) may be effectively incorporated into conditioning therapy before transplant for patients with refractory/relapsed malignant lymphoma. We investigated the feasibility of debulking selective lymph node irradiation before autologous and/or allogeneic stem cell transplantation (SCT) using helical tomotherapy (HT).nnnMETHODS AND MATERIALSnSix consecutive patients with refractory malignant lymphoma were referred to our institution for salvage HT before SCT. All patients had been previously heavily treated but had bulky residual tumor despite chemotherapy (CT) intensification. Two patients had received previous radiation therapy. HT delivered 30-40 Gy in the involved fields (IF), using 6 MV photons, 2 Gy per daily fraction. Total duration of treatment was 28 to 35 days.nnnRESULTSnUsing HT, doses to critical organs (heart, lungs, esophagus, and parotids) were significantly decreased and highly conformational irradiation could be delivered to all clinical target volumes. HT delivery was technically possible, even in patients with lesions extremely difficult to irradiate in other conditions or in patients with previous radiation therapy. No Grade 2 or higher toxicity occurred. Four months after the end of HT, 5 patients experienced complete clinical, radiologic, and metabolic response and were subsequently referred for SCT.nnnCONCLUSIONSnBy more effectively sparing critical organs, HT may contribute to improving the tolerance of debulking irradiation before allograft. Quality of life may be preserved, and doses to the heart may be decreased. This is particularly relevant in heavily treated patients who are at risk for subsequent heart disease. These preliminary results require further prospective assessment.

Concurrent involved field radiation therapy and temsirolimus in refractory mantle cell lymphoma (MCL).

Temsirolimus, an inhibitor of mammalian target of rapamycin, has antitumor activity and improves progress-free survival in patients with relapsed or refractory mantle cell lymdhoma (MCL) [1,2]. Helical tomotherapy (HT) is an irradiation modality, which combines accurate patient positioning and intensity-modulated fan-beam radiotherapy (RT) [3– 5]. Because of highly conformal dose distribution, it improves sparing of critical organs. This is particularly relevant in heavily treated patients who are at risk for subsequent toxicities [3]. This work is reporting the first case in the literature of concurrent use of Temsirolimus and RT in patient before bone marrow transplantation (BMT). A 47-year-old male patient treated since 2003 for Stage IV refractory MCL with over expression of D1 gene and t(11; 14) translocation, was referred in our Department. The patient had been heavily previously treated and had received: six lines chemotherapy, two total body irradiations, one autologous stem cell transplantation, and one allogeneic cord blood transplantation. He experienced lymph node (inguinal and lombo-aortic iliac) and bone marrow relapse in January 2009 and was treated with VELCAD-ARACYTIN-DXM 3 three cycles, follow by RCHOP and VELCADE, then REVLIMID with DXM with persistence of the lymph nodes in low mediastinum, lomboaortic, iliac, and inguinal lymph nodes. New treatment protocol using Temsirolimus as previously reported [2] was offered to the patient and at the same time, he was addressed in our Department for debulking HT before new allogeneic cord blood transplant. The patient received 36 Gy in 18 fractions concurrently with Temsirolimus. The dose distribution is shown in Image 1. The patient was followed weekly clinically and biologically by his radiation oncologist. The clinical tolerance was perfect without any symptoms. The only observed toxicity was Grade III thrombopenia as reported in 59% of patients treated with this protocol of Temsirolimus [2]. Two months after the end of RT, the patient experienced very good response objectived by CT scan and positron emission tomography (PET). Currently, he is ECOG 0 and is prepared for his transplant. This first report shows the efficacy and feasibility of concurrent Temsirolimus and HT as a therapeutic option in relapsed or refractory MCL. Prospective studies are needed to confirm this result. References 1. Ruan J, Coleman M, Leonard JP. Management of relapsed mantle cell lymphoma: Still a treatment challenge. Oncology (Williston Park) 2009;23:683– 690. 2. Hess G, Herbrecht R, Romaguera J, et al. Phase III study to evaluate temsirolimus compared with investigator’s choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 2009;27:3822–3829. 3. Chargari C, Vernant JP, Tamburini J, et al. Feasibility of helical tomotherapy for debulking irradiation prior to stem cell transplantation in malignant lymphoma. Int J Radiat Oncol Biol Phys, in press. 4. Chargari C, Kirova YM, Zefkili S, et al. Solitary plasmocytoma: Improvement in critical organs sparing by means of helical tomotherapy. Eur J Haematol 2009;83:66–71. 5. Chargari C, Zefkili S, Kirova YM. Potential of helical tomotherapy in critical organs sparing in AIDS patient treated for Hodgkin’s lymphoma. Clin Infect Dis 2009;48:687–689. Image 1. Dose distribution, the colors are corresponding to the dose distribution,

Severe acute radiation-related skin toxicity in a breast cancer patient with Behçet’s disease

conformality (Fig. 1C). The use of one unique field including both chest wall and IMC volumes solved the problem of junction between these two areas. To ensure a sufficient skin dose, a bolus of 5 mmwas used. Electron energy was chosen so that the 95% isodose (47.5 Gy) was situated at the costal wall depth. Electron-beam radiotherapy of the chest wall with lymph node irradiation using the presented technique seems well adapted and safe for this rare population of patients.

The role of helical tomotherapy in the treatment of bone plasmacytoma

We evaluated the early clinical outcome of patients with solitary bone plasmacytoma (SP) or a solitary lesion of multiple myeloma (MM) treated with helical tomotherapy (HT) compared with 3D conformal radiotherapy (3D-CRT), in terms of target coverage and exposure of critical organs. Ten patients with SP and 3 patients with a solitary lesion of MM underwent radiation therapy (RT) delivered by HT, to a dose of 40 Gy in 20 fractions. Treatment planning was then performed with 3D-CRT and the dosimetric parameters of both techniques were compared. Patients were also assessed for response to treatment and acute toxicities. With a median follow-up of 13 months, 78% of patients with pain before RT had resolution of their symptoms. Coverage of target lesion was adequate with both techniques in 12 of 13 patients. Target coverage was significantly lower for HT (V(95%) = 98.55% vs. 97.15%; p = 0.04, for 3D-CRT and HT, respectively). Target overdoses were also lower with HT (V(105%) = 2.01% vs. 0.19%; p= 0.16), although nonsignificant. Finally, there were no significant differences in organs-at-risk irradiation between both techniques. The early treatment tolerance was excellent, with no toxicity higher than grade I. RT of SP and MM with a solitary lesion can be safely delivered with HT, with no major acute side effects and good symptomatic control. Finally, HT provides a dosimetry similar to that of 3D-CRT in terms of organs-at-risk sparing and target volume coverage.