Adjuvant radiotherapy in the management of axillary node negative invasive breast cancer: a qualitative systematic review.

PURPOSE: To actualize and to detail guidelines used in technical radiotherapy and indications for innovative radiation technologies in early axillary node negative breast cancer (BC). METHODS: Dosimetric and treatment planning studies, phase II and III trials, systematic reviews and retrospective studies were all searched (Medline(®) database). Their quality and clinical relevance were also checked against validated checklists. A level of evidence was associated for each result. RESULTS: A total of 75 references were included. Adjuvant BC radiotherapy (50Gy/25 fractions/5 weeks followed by a tumor boost of 16Gy/8 fractions) is still the standard of care. Overall treatment time could be shortened for patients who present with low local relapse risk BC by using either hypofractionated whole breast irradiation; or accelerated partial breast irradiation. BC IMRT is not used in current practice. CONCLUSION: Our group aimed to provide guidelines for technical and clinical applications of innovative BC radiation technologies.

Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study.

BACKGROUND: Trastuzumab (T) combined with chemotherapy has been recently shown to improve outcome in HER2-positive breast cancer (BC). The aim of this study was to evaluate the toxic effects of concurrent radiation therapy (RT) and T administration in the adjuvant setting. PATIENTS AND METHODS: Data of 146 patients with stages II-III HER2-positive BC were recorded. Median age was 46 years. In all, 32 (23%) and 114 (77%) patients received a weekly and a 3-week T schedule, respectively. A median dose of 50 Gy was delivered after surgery. Internal mammary chain (IMC) was irradiated in 103 (71%) patients. RESULTS: Grade >2 dermatitis and esophagitis were noted in 51% and 12%, respectively. According to the Common Toxicity Criteria v3.0 scale and HERA (HERceptin Adjuvant) trial criteria, respectively, 10% and 6% of the patients had a grade >/=2 of left ventricular ejection fraction (LVEF) decrease after RT. Multivariate analyses revealed two independent prognostic factors: weekly T administration (for LVEF decrease) and menopausal status (for dermatitis). Higher level of T cumulative dose (>1600 mg) was only borderline of statistical significance for acute esophagitis toxicity. CONCLUSION: We showed that weekly concurrent T and RT are feasible in daily clinical practice with, however, a decrease of LVEF. Cardiac volume sparing and patient selections for IMC irradiation are highly recommended. Longer follow-up is warranted to evaluate late toxic effects.

[Adjuvant combined radiochemotherapy: a feasibility study of a new strategy in stages I and II]. / Traitement adjuvant des cancers du sein par radiochimiothérapie concomitante: étude de faisabilité d'une nouvelle alternative stratégique dans les stades I et II.

Adjuvant radiotherapy is the rule after conservative surgery for breast cancer. Furthermore, an anthracycline-based chemotherapy is recommended in node-positive patients and in poor prognosis tumors. The optimal schedule of treatment has yet to be determined, but ideally, none of these therapeutic modalities should be delayed. We have therefore conducted a feasibility trial using post-operative concurrent chemoradiation therapy with an anthracenedione. Between May 1990 and October 1994, 154 patients with stage I or II breast cancer who had benefited of either limited or radical surgery were treated with adjuvant concurrent chemoradiotherapy. Radiotherapy consisted of 50 Gy in 25 fractions over 5 weeks to the chest wall or the breast, and to the supraclavicular and internal mammary lymph nodes. When indicated, a boost of 15 Gy was then delivered to the primary tumor bed (n = 75). Starting on the first week of radiotherapy, combined chemotherapy with 5-fluorouracil, mitoxantrone, and cyclophosphamide was administered at 21-day intervals, for 4 to 6 cycles. Compliance to therapy was excellent. Median radiotherapy dose was 49.5 Gy to the chest wall or breast, and to the lymph nodes, and 14.2 Gy to the tumor bed. Chemotherapy was given at full dose in over 80% of the cases and the 21-day interval between cycles was respected in 31%. In 45% of the cases, a 28-day interval was required due to toxicity, and at least one interval longer than 28 days was necessary in the remainder of the patients. Main toxicities were nausea and vomiting (20.8%) and grade 3-4 neutropenia (12.3%). Grade 1 cutaneous toxicity occurred in 62.3% of the cases, and severe grade 3 radiation dermatitis requiring temporary interruptions of therapy in 4.5%. With the exception of one case of grade 3 acute cardiac toxicity, there was no other severe side-effects. In conclusion, this pilot study demonstrates the feasibility of concurrent chemoradiation therapy with an anthracenedione for stage I and II breast cancer in the adjuvant setting. Whether this approach compares favorably with standard sequential therapy in terms of long-term results remains to be determined and should be assessed in a phase III trial.

Ophthalmological study of the lesions induced by the filarial worm with dermal microfilariae, Monanema martini, in its murid hosts.

The filaria Monanema martini with skin-dwelling microfilariae induces in its natural murid hosts lesions similar to those in human onchocerciasis. This was demonstrated by histo-pathological studies but it appeared useful to evaluate the model by a clinical investigation. An ophthalmological analysis was performed on the two species of hosts, inoculated by one, two, or multiple doses of larvae, and with infections of at least one year duration. A total of 140 eyes was examined (anterior and posterior segments). We established a system for enumerating the different types and severities of lesions. We prepared a file for each eye and attempted to quantify our observations. The significant lesions were different in the two host species. In Arvicanthis niloticus, in which motile microfilariae were seen in the anterior segment, punctate keratitis was predominant. In Lemniscomys striatus, the posterior segment showed complete chorioretinal atrophy, similar to the final stage of onchocercal chorioretinitis in humans. M. martini represents in its natural hosts two complementary models for the study of the pathogenesis and treatment of human onchocerciasis.

Onchocerca-like lesions induced by the filarioid nematode Cercopithifilaria johnstoni, in its natural hosts and in the laboratory rat.

Histo-pathological analysis of the eyes, ears, skin and associated skeletal muscles of the back of 14 animals infected with a filarioid worm with dermal microfilariae, Cercopithifilaria johnstoni: seven Rattus fuscipes, of which four were naturally infected, two marsupials, Perameles nasuta and Isodon macrourus, and five R. norvegicus. This filarioid nematode induces skin and eye lesions in all the infected animals. These lesions are similar to those described earlier with other filarioid species with dermal microfilariae, such as Monanema martini and Onchocerca volvulus; the pathogeny is similar: microfilariae live inside the lymphatic vessels and their accidental exit gives rise to a localized inflammatory reaction leading to fibrosis. C. johnstoni is particularly interesting because it may be adapted to the laboratory rat, and because the ocular lesions are severe.

Quality control of radiotherapeutic treatment of medulloblastoma in a multicentric study: the contribution of radiotherapy technique to tumour relapse. The French Medulloblastoma Group.

Between 06.86 and 11.89, 88 medulloblastoma or primitive neuroectodermic tumour (PNET) localised in the posterior fossa have been included in the M7 multicentric protocol, 82 received the totality of the radiotherapy treatment and were evaluable for this study. Twenty-two of these 82 patients relapsed: their radiotherapy treatment is analysed in the present study. In 10 cases out of the 22 relapses treatment failure was probably due to a radiotherapeutic imperfection. This study confirms the necessity of a strict radiotherapy control, particularly in multicentric study.

Veno-occlusive disease in children after intensive chemo- and radiotherapy and repeated halothane anesthesias. A report of 2 cases.

Two cases of veno-occlusive disease (VOD) occurring in metastatic neuroblastoma patients are reported. Treatment included a remission induction by conventional chemotherapy and surgery followed by an early consolidation with massive chemotherapy, total body irradiation and cleared autologous bone marrow transplantation (ABMT). Both patients had multiple halothane anesthesias. Liver complications occurred 10 and 21 days respectively after ABMT. The first patient had a precocious and severe clinical and biological VOD, heparinotherapy and symptomatic treatment were ineffective and he died 12 days after ABMT. The second patient had a moderate and later syndrome which was controlled by heparin therapy (100 U/kg/day) delivered by continuous infusion; he is now alive free of hepatic disturbance 28 months after ABMT. The potential iatrogenic factors are discussed, with special focus on the use of halogenated anesthetic drugs.