Hydrosorb® versus control (water based spray) in the management of radio-induced skin toxicity: Results of multicentre controlled randomized trial.

PURPOSE: To report the efficacy of Hydrosorb® versus control (water based spray) as topical treatment of grade 1-2 radiodermatitis in patients (pts) treated for early stage breast cancer (BC) with normo fractionated radiotherapy (RT). PATIENTS AND METHODS: BC pts were randomized to receive either Hydrosorb® (A) or water based spray (B). The primary endpoint was local treatment failure defined as interruption of RT because of skin radiotoxicity or change of local care because of skin alteration. Secondary endpoints were: evaluation of skin colorimetry, pain, quality of life. RESULTS: Two-hundred seventy-eight pts were enrolled. There were 186 successfully treated pts. There were 60 "failures" in the Hydrosorb® arm, and 62 in the control arm (p=0.72), but mostly without interruption of the RT. Twenty-four pts stopped RT for local care. The average absolute reduction of colorimetric levels between day 28 and day 0 was 4 in the Hydrosorb®, and 4.2 in the water spray groups, respectively (p=0.36). Forty-eight patients in the Hydrosorb® arm had a VAS >2 versus 51 pts in the placebo arm, i.e. 34% and 38%, respectively (p=0.45). A significant reduction of pain was observed on D7 and D21 in the Hydrosorb® arm. CONCLUSIONS: The present study showed no significant difference between Hydrosorb® and simple water spray in the treatment of acute radio-induced dermatitis even if there was a trend to an improvement in pain at the first weeks after the treatment. Systematic prevention measures and modern breast cancer radiotherapy techniques now allow excellent tolerability, but the place of topical treatment to optimize this tolerability has yet to be defined. It seems that the most important part of the skin care is the prevention of skin reactions using new adapted techniques, as well as strict hygiene.

Choroidal melanoma: does endoresection prevent neovascular glaucoma in patient treated with proton beam irradiation?

PURPOSE: To evaluate the efficacy of endoresection after proton beam radiotherapy to prevent neovascular glaucoma (NVG) in patients treated for choroidal melanoma. METHODS: From a series of 4,867 patients treated for choroidal melanoma were prospectively recorded in the database (Macro Infermed 3.075). One hundred and seventy-one patients presenting a tumor diameter >10 mm and thickness >5 mm treated with proton beam (PB) radiotherapy were selected. One group of 63 patients was treated with PB therapy followed by endoresection (PE) of the scar. This group was compared with 2 historical matched controlled groups: 57 patients treated with PB therapy alone (P) and 51 patients treated with PB therapy followed by transpupillary thermotherapy of the scar (PTTT). Main outcome measures are as follows: age, gender, tumor diameter, tumor thickness, pre- and posttreatment visual acuity, NVG rate, secondary enucleation rate, and 5-year survival. Statistical analysis was performed using R version 2.5.1 software. RESULTS: Correlations between the 3 groups were P = 0.29 for age, P = 4.7×10 for tumor diameter, and P = 6.44×10 for tumor thickness. Comparison between the 3 groups showed that 2-year survival without secondary enucleation was 96.2% for PE, 88.8% for P, and 98% for PTTT (P = 0.203) (95% confidence interval). Two-year survival without NVG (95% confidence interval) was 92.7% (85.1-1.00) for PE, 54.6% for P, and 62.1% for PTTT (P = 0.0001). The difference between the endoresection (PE) group and the PB radiotherapy (P) and PB radiotherapy + TTT (PTTT) groups in terms of reduction of the NVG rate was statistically significant. Relative risk of developing NVG was calculated with the P group as reference, relative risk = 1. The relative risk of the PTTT group was 0.79 (20% reduction of the risk), and the relative risk of the PE group was 0.18 (82% reduction of the risk of developing NVG). CONCLUSION: This study shows that endoresection of the necrotic scar after PB radiotherapy reduces the risk of NVG and secondary enucleation for selected choroidal melanoma patients.

Prospective and comparative evaluation of the toxicity of adjuvant concurrent chemoradiotherapy after neoadjuvant chemotherapy for breast cancer.

PURPOSE: The lack of pathologic breast cancer response to neoadjuvant chemotherapy (NCT), a negative prognostic factor, has prompted the addition of chemotherapy to adjuvant radiotherapy. This study aims to investigate prospectively the toxicities of adjuvant concurrent chemoradiotherapy versus radiotherapy alone. PATIENTS AND METHODS: Two groups of patients treated for breast cancer between 1997 and 2002 by NCT, surgery, and radiotherapy with or without concurrent chemotherapy, were matched on age, body mass index (BMI), treatment period, treated side, and surgery type. Late toxicity was prospectively evaluated according to the CTCAE v3.0. Acute toxicity was derived from the medical charts. RESULTS: A total of 52 patients were matched. Median follow-up was 10 years. Acute toxicity was higher in the chemoradiotherapy group compared with the radiotherapy alone group: 37% patients versus 10% experienced a grade 2/3 epithelitis (P=0.002); 48% versus 8% experienced a grade ≥1 mucositis (P=0.00001). Late toxicity was not significantly different in both univariate (51% vs. 49%; P=0.79) and multivariate analyses adjusted on the BMI (P=0.08). In univariate analysis, only the BMI tended to be predictive of toxicity (P=0.07). CONCLUSIONS: Concurrent chemoradiotherapy after NCT and surgery was associated with increased acute toxicity but not long-term toxicity. The efficacy of this therapeutic strategy should be evaluated to better define its indications.

Treatment of uveal melanoma by accelerated proton beam.

Proton beam irradiation of uveal melanoma has great advantages compared to brachytherapy because of the homogenous dose delivered to the tumor and the possibility of sparing normal tissue close to the tumor. We describe the technique of proton beam therapy including the surgical technique of clip positioning, the radiotherapy delivery technique and the dose administered (60 Gy cobalt relative biological effectiveness in 4 fractions). Indications of proton beam are given and the follow-up procedure is described. An inactive residual tumor scar is observed after 2-3 years. Results are given comparing the most recent series of patients treated at the Institut Curie-Orsay proton therapy center with the data published in the literature. The metastasis rate at 10 years varies between 25 and 30%. Local control is excellent. The local recurrence rate at 10 years is usually around 5%. Secondary enucleation is performed in 10-15% of patients either due to complications or local recurrence. Complications such as retinal detachment, maculopathy, papillopathy, cataract, glaucoma, vitreous hemorrhage and dryness are described. The severest complication that usually leads to secondary enucleation is neovascular glaucoma and it is encountered after irradiation of large to extra-large tumors. The toxic tumor syndrome has recently been described. It is hypothesized that the residual tumor scar may produce proinflammatory cytokines and VEGF leading to intraocular inflammation and neovascular glaucoma. Additional treatments after proton beam such as transpupillary thermotherapy, endoresection of the tumor scar or intravitreal injections of anti-VEGF may reduce the rate of these complications.

Preoperative radio-chemotherapy in early breast cancer patients: long-term results of a phase II trial.

PURPOSE: This phase II trial aimed to investigate the efficacy of concurrent radio- (RT) and chemotherapy (CT) in the preoperative setting for operable, non-metastatic breast cancer (BC) not amenable to initial breast-conserving surgery (BCS). PATIENTS AND METHODS: From 2001 to 2003, 59 women were included. CT consisted of four cycles of 5-FU, 500 mg/m(2)/d, continuous infusion (d1-d5) and vinorelbine, 25 mg/m(2) (d1 and d6). Starting concurrently with the second cycle, RT delivered 50 Gy to the breast and 46 Gy to the internal mammary and supra/infra-clavicular areas. Breast surgery and lymph node dissection were then performed. Adjuvant treatment consisted of a 16 Gy boost to the tumor bed after BCS, FEC (four cycles of fluorouracil 500 mg/m(2), cyclophosphamide 500 mg/m(2), and epirubicin 100 mg/m(2), d1; d21) for pN1-3 and hormone-therapy for positive hormone receptors BC. RESULTS: The in-breast pathological complete response rate was 27%. BCS was performed in 41 (69%) pts. Overall and distant-disease free survivals at 5 years were respectively 88% [95% CI 80-98] and 83% [95% CI 74-93] whereas locoregional and local controls were 90% [95% CI 82-97] and 97% [95% CI 92-100]. Late toxicity (CTCAE-V3) was assessed in 51 pts (86%) with a median follow-up of 7 years [5-8]. Four (8%) experienced at least one grade III toxicities (one telangectasia and three fibroses). Cosmetic results, assessed in 35 of the 41 pts (85%) who retained their breasts, were poor in four pts (11%). CONCLUSION: Preoperative concurrent administration of RT and CT is an effective regimen. Long-term toxicity is moderate. This association deserves further evaluations in prospective trials.

Treatment of mucosa-associated lymphoid tissue-type ocular adnexal lymphoma.

New data have recently been reported in ocular adnexal lymphomas (OALs), particularly of mucosa-associated lymphoid tissue (MALT)-type, regarding their biological characteristics and therapeutic management. A possible association between OAL and Chlamydia psittaci infection has suggested new mechanisms of lymphomagenesis and opened the way for specific targeted treatment. Similarly, the place of rituximab monoclonal antibody therapy and more conventional chemotherapy, as well as a 'wait-and-see' policy in few clearly defined situations, must be defined in relation to the standard treatment option consisting of radiotherapy for low-grade lymphomas. The aims of this review are therefore to present the various treatment modalities and to discuss the place of each modality in the management of ophthalmologic lymphomas.

Conservative treatments of intraocular retinoblastoma.

OBJECTIVE: To describe the efficacy of conservative management of retinoblastoma by an association of conservative ocular therapies and chemothermotherapy. DESIGN: Phase II prospective nonrandomized trial. PARTICIPANTS: Eighty-three children were included (115 eyes). METHODS: Conservative ocular therapies and chemothermotherapy (intravenous carboplatin followed by transpupillary thermotherapy to the tumor) after chemoreduction by 2 cycles of carboplatin and etoposide. MAIN OUTCOME MEASURES: Use of external beam therapy and ocular tumor control. RESULTS: One hundred fifteen of the 147 affected eyes were eligible for conservative management. Nineteen children had unilateral lesions (22.8%), and 64 (77.1%) had bilateral lesions. Sixty-six children received neoadjuvant chemotherapy before ocular therapy, which consisted of one or a combination of several techniques: chemothermotherapy (65 children [86 eyes]) with a mean of 3 cycles per child, thermotherapy alone (22 children [24 eyes]), cryoapplication (49 children [58 eyes]), and iodine 125 brachytherapy (26 children [29 eyes]). Tumor control was achieved for 97 eyes (84%). At the end of the study, external beam radiotherapy (EBR) was necessary for a total of 9 children (11%) and 13 eyes (12%). Enucleation was necessary for a total of 23 eyes (20%), because of complications in 5 cases. CONCLUSIONS: Neoadjuvant chemotherapy with 2 cycles of carboplatin and etoposide followed by ocular therapy and chemothermotherapy achieves satisfactory tumor control and permits a low need for EBR.

Ocular adnexal lymphoma: a review of clinicopathologic features and treatment options.

The recent literature shows that interest in ocular adnexal lymphomas and their biologic and clinical characteristics--along with their possible association with Chlamydia psittaci infection and therapeutic management with rituximab or anti-Chlamydia psittaci antibiotic therapy--is considerable. These new data have modified the previously reported features of this disease and have made an updated review of the literature necessary. The aims of this review are to present the current knowledge on the biology of these lymphomas, their clinical features and prognostic factors, and the panel of all available treatment options.